A Rapid and Accurate UHPLC Method for Determination of Monosaccharides in Polysaccharides of Different Sources of Radix Astragali and Its Immune Activity Analysis.

With the escalating demand for Astragalus polysaccharides products developed from Radix Astragali (RA), the necessity for quality control of polysaccharides in RA has become increasingly urgent. In this study, a specific method for the simultaneous determination of seven monosaccharides in polysaccharides extracted from Radix Astragali (RA) has been developed and validated using ultra-performance liquid chromatography equipped with an ultraviolet detector (UHPLC-UV) for the first time. The 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatizations were separated on a C18 column (Waters ACQUITYTM, Milfor, MA, USA, 1.8 µm, 2.1 × 100 mm) using gradient elution with a binary system of 5 mm ammonium formate (0.1% formic acid)-acetonitrile for 24 min. Additionally, seven monosaccharides showed good linear relationships (R2, 0.9971-0.9995), adequate precision (RSD < 4.21%), and high recoveries (RSD < 4.70%). The established method was used to analyze 109 batches of RA. Results showed that the Astragalus polysaccharides (APSs) mainly consist of mannose (Man), rhamnose (Rha), glucose (Glu), galactose (Gal), arabinose (Ara), xylose (Xyl); and fucose (Fuc); however, their composition was different among RA samples from different growth patterns, species, growth years, and origins, and the growth mode of RA and the age of wild-simulated RA can be accurately distinguished by principal component analysis (PCA). In addition, the immunological activity of APSs were also evaluated jointly by measurement of the NO release with RAW264.7, with the results showing that APSs have a promoting effect on the release of NO and exhibit a significant correlation with Man, Glu, Xyl, and Fuc contents. Accordingly, the new established monosaccharides analytical method and APS-immune activity determination in this study can provide a reference for quality evaluation and the establishment of quality standards for RA.

Spatial distribution and health risks assessment of heavy metals in e-waste dumping sites from Pakistan.

The present study focused on to determine the concentration and health risk of heavy metals (Cu, Pb, Zn, Cd, Hg, Cr) in e-waste contaminated soils collected from different provinces of Pakistan. Further, the impact of heavy metals on soil enzyme activities and microbial community was also investigated. The concentration (mg/kg) of Hg, Zn, Fe, Cu, Pb, Cd, and Cr ranged between 0-0.258, 2.284-6.587, 3.005-40.72, 8.67-36.88, 12.05-35.03, 1.03-2.43, and 33.13-60.05, respectively. The results revealed that Lahore site of Punjab province indicated more concentration of heavy metals as compared to other sites. The level of Cr at all sites whereas Hg at only two sites exceeds the World Health Organization standards (WHO) for soil. Soil enzyme activity exhibited dynamic trend among the sites. Maximum enzyme activity was observed for urease followed by phosphatase and catalase. Contamination factor (Cf), Pollution load index (PLI), and geo-accumulation index (Igeo) results showed that all the sites are highly contaminated with Cu, Cd, and Pb. Hazard index (HI) was less than 1 for children and adults suggesting non-carcinogenic health risk. Principle component analysis results depicted relation among Cr, Fr, catalase, and actinomycetes; Cd, OM, urease, and bacteria, and Pb, Cu, Zn, Hg, and phosphatase, suggesting soil enzymes and microbial community profiles were influenced by e-waste pollution. Therefore, there is a dire need to introduce sustainable e-waste recycling techniques as well as to make stringent e-waste management policies to reduce further environmental contamination.

Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway.

PURPOSE: Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation. METHODS: C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. RESULTS: Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol. CONCLUSIONS: Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Moderate precipitation reduction enhances nitrogen cycling and soil nitrous oxide emissions in a semi-arid grassland.

The ongoing climate change is predicted to induce more weather extremes such as frequent drought and high-intensity precipitation events, causing more severe drying-rewetting cycles in soil. However, it remains largely unknown how these changes will affect soil nitrogen (N)-cycling microbes and the emissions of potent greenhouse gas nitrous oxide (N2 O). Utilizing a field precipitation manipulation in a semi-arid grassland on the Loess Plateau, we examined how precipitation reduction (ca. -30%) influenced soil N2 O and carbon dioxide (CO2 ) emissions in field, and in a complementary lab-incubation with simulated drying-rewetting cycles. Results obtained showed that precipitation reduction stimulated plant root turnover and N-cycling processes, enhancing soil N2 O and CO2 emissions in field, particularly after each rainfall event. Also, high-resolution isotopic analyses revealed that field soil N2 O emissions primarily originated from nitrification process. The incubation experiment further showed that in field soils under precipitation reduction, drying-rewetting stimulated N mineralization and ammonia-oxidizing bacteria in favor of genera Nitrosospira and Nitrosovibrio, increasing nitrification and N2 O emissions. These findings suggest that moderate precipitation reduction, accompanied with changes in drying-rewetting cycles under future precipitation scenarios, may enhance N cycling processes and soil N2 O emissions in semi-arid ecosystems, feeding positively back to the ongoing climate change.

Kv1.3 Blockade Alleviates White Matter Injury through Reshaping M1/M2 Phenotypes via the NF-κB Signaling Pathway after Intracerebral Hemorrhage.

BACKGROUND: White matter injury (WMI) in basal ganglia usually induces long-term disability post intracerebral hemorrhage (ICH). Kv1.3 is an ion channel expressed in microglia and induces neuroinflammation after ICH. Here, we investigated the functions and roles of Kv1.3 activation-induced inflammatory response in WMI and the Kv1.3 blockade effect on microglia polarization after ICH. METHODS: Mice ICH model was constructed by autologous blood injection. The expression of Kv1.3 was measured using immunoblot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays. Then, the effect of administration of 5-(4-Phenoxybutoxy) psoralen (PAP-1), a selectively pharmacological Kv1.3 blocker, was investigated using open field test (OFT) and basso mouse score (BMS). RT-qPCR, immunoblot, and enzyme-linked immunosorbent assay (ELISA) were taken to elucidate the expression of pro-inflammatory or anti-inflammatory factors around hematoma. PAP-1's function in regulating microglia polarization was investigated using immunoblot, RT-qPCR, and immunostaining assays. The downstream PAP-1 signaling pathway was determined by RT-qPCR and immunoblot. RESULTS: Kv1.3 expression was increased in microglia around the hematoma significantly after ICH. PAP-1 markedly improved neurological outcomes and the WMI by reducing pro-inflammatory cytokine accumulation and upregulating anti-inflammatory factors. Mechanistically, PAP-1 reduces NF-κB p65 and p50 activation, thus facilitating microglia polarization into M2-like microglia, which exerts this beneficial effect. CONCLUSIONS: PAP-1 reduced pro-inflammatory cytokines accumulation and increased anti-inflammatory factors by facilitating M2-like microglia polarization via the NF-κB signaling pathway. Thus, the current study shows that the Kv1.3 blockade is capable of ameliorating WMI by facilitating M2-like phenotype microglia polarization after ICH.

Discrimination of Radix Astragali from Different Growth Patterns, Origins, Species, and Growth Years by an H1-NMR Spectrogram of Polysaccharide Analysis Combined with Chemical Pattern Recognition and Determination of Its Polysaccharide Content and Immunological Activity.

The fraud phenomenon is currently widespread in the traditional Chinese medicine Radix Astragali (RA) market, especially where high-quality RA is substituted with low-quality RA. In this case, focused on polysaccharides from RA, the classification models were established for discrimination of RA from different growth patterns, origins, species, and growth years. 1H Nuclear Magnetic Resonance (H1-NMR) was used to establish the spectroscopy of polysaccharides from RA, which were used to distinguish RA via chemical pattern recognition methods. Specifically, orthogonal partial least squares discriminant analysis (OPLS-DA) and linear discriminant analysis (LDA) were used to successfully establish the classification models for RA from different growth patterns, origins, species, and growth years. The satisfactory parameters and high accuracy of internal and external verification of each model exhibited the reliable and good prediction ability of the developed models. In addition, the polysaccharide content and immunological activity were also tested, which was evaluated by the phagocytic activity of RAW 264.7. And the result showed that growth patterns and origins significantly affected the quality of RA. However, there was no significant difference in the aspects of origins and growth years. Accordingly, the developed strategy combined with chemical information, biological activity, and multivariate statistical method can provide new insight for the quality evaluation of traditional Chinese medicine.

Isolation and Identification of Chemical Compounds from Agaricus blazei Murrill and Their In Vitro Antifungal Activities.

This study explores the antifungal properties of Agaricus blazei Murrill, a valuable medicinal and edible fungus. Six compounds (1-6) were first isolated from A. blazei using various isolation techniques and identified using spectroscopic methods. These compounds include linoleic acid, 1,1'-oxybis(2,4-di-tert-butylbenzene), glycerol monolinoleate, volemolide (17R)-17-methylincisterol, (24s)-ergosta-7-en-3-ol, and dibutyl phthalate. This study also assesses the antifungal activities of these compounds against Trichophyton mentagrophology, Trichophyton rubrum, Candida albicans, and Cryptococcus neoformans. The results demonstrate varied sensitivities against these pathogenic fungi, with compound 2 showing significant inhibition against T. mentagrophology, compound 3 showing significant inhibition against T. rubrum, and compound 6 showing significant inhibition against C. albicans. This study underscores the medicinal potential of A. blazei as an antifungal agent and sheds light on its valuable research implications.

Classification and Authentication of Lonicerae Japonicae Flos and Lonicerae Flos by Using 1H-NMR Spectroscopy and Chemical Pattern Recognition Analysis.

Lonicerae japonicae flos and Lonicerae flos are increasingly widely used in food and traditional medicine products around the world. Due to their high demand and similar appearance, they are often used in a confused or adulterated way; therefore, a rapid and comprehensive analytical method is highly required. In this case, the comparative analysis of a total of 100 samples with different species, growth modes, and processing methods was carried out by nuclear magnetic resonance (1H-NMR) spectroscopy and chemical pattern recognition analysis. The obtained 1H-NMR spectrums were employed by principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and linear discriminant analysis (LDA). Specifically, after the dimensionality reduction of data, linear discriminant analysis (LDA) exhibited good classification abilities for the species, growth modes, and processing methods. It is worth noting that the sample prediction accuracy from the testing set and the cross-validation predictions of the LDA models were higher than 95.65% and 98.1%, respectively. In addition, the results showed that macranthoidin A, macranthoidin B, and dipsacoside B could be considered as the main differential components of Lonicerae japonicae flos and Lonicerae Flos, while secoxyloganin, secologanoside, and sweroside could be responsible for distinguishing cultivated and wild Lonicerae japonicae Flos. Accordingly, 1H-NMR spectroscopy combined with chemical pattern recognition gives a comprehensive overview and provides new insight into the quality control and evaluation of Lonicerae japonicae flos.

Increased risk of nonrelapse mortality post T-cell-replete haploidentical stem cell transplantation in patients with recurrence of acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) causes significant morbidity and mortality. While most studies focus on classic or late aGVHD, some patients with previous aGVHD achieve complete remission and later develop another episode of aGVHD. Data on recurrence of aGVHD (RaGVHD) are lacking. This study aimed to identify the incidence, risk factors, and impacts of RaGVHD after T-cell-replete haploidentical hematopoietic cell transplantation (haplo-HCT) without posttransplantation cyclophosphamide. We evaluated patients with RaGVHD after haplo-HCT between 2017 and 2019 and compared their outcomes to those of patients with no aGVHD and those of patients with one episode of de novo aGVHD. Of 199 patients included in the analysis, 45 experienced 50 cases of RaGVHD with a 1-year cumulative incidence of 19.0% (95% CI: 14.5-24.6). Grade III-IV aGVHD was more common in RaGVHD than in previous aGVHD (22.2% vs. 4.4%, p = 0.01). Female donor to male recipient was strongly associated with RaGVHD (HR: 2.5, p = 0.009). The most common death in patients with RaGVHD was GVHD-related, which was different from controls who mostly died from relapse (p = 0.008). RaGVHD was an independent risk factor for chronic GVHD (HR: 2.6, p = 0.006) and nonrelapse mortality (HR: 2.4, p = 0.019) and a significant predictor of lower GVHD relapse-free survival (HR: 1.9, p = 0.020) and cGVHD relapse-free survival (HR: 2.1, p = 0.007). In conclusion, clinical manifestations and negative impacts of RaGVHD needs to be recognized independently.

An NF-κB-responsive long noncoding RNA, PINT, regulates TNF-α gene transcription by scaffolding p65 and EZH2.

Long noncoding RNAs (lncRNAs) are central regulators of the inflammatory response and play an important role in inflammatory diseases. PINT has been reported to be involved in embryonic development and tumorigenesis. However, the potential functions of PINT in the innate immune system are largely unknown. Here, we revealed the transcriptional regulation of inflammatory genes by PINT, whose expression is primarily dependent on the NF-κB signaling pathway in human and mouse macrophage and intestinal epithelial cell lines. Functionally, PINT selectively regulates the expression of TNF-α in basal and LPS-stimulated cells. Mechanistically, PINT acts as a modular scaffold of p65 and EZH2 to coordinate their localization and specify their binding to the target genes. Further, a high expression level of PINT was detected in intestinal mucosal tissues from patients with ulcerative colitis (UC). Together, these findings demonstrate that PINT acts as an activator of inflammatory responses, highlighting the importance of this lncRNA as a potential therapeutic target in infectious diseases and inflammatory diseases.

Eltrombopag in the treatment of patients with persistent thrombocytopenia after haploidentical peripheral blood stem cell transplantation: a single-center experience.

Persistent thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of bleeding and poor survival. The exact pathogenesis underlying PT remains unclear, and its management is difficult. Here we conducted a retrospective study to evaluate the efficacy and safety of eltrombopag (EPAG) in 34 patients with PT after allo-HSCT. Seven patients suffered from prolonged isolated thrombocytopenia (PIT), and 27 had secondary failure of platelet recovery (SFPR). For most patients, the initial dose was 25 mg or 50 mg daily, then adjusted to the maximum dose of 50-100 mg per day according to the response of platelet recovery and toleration of patients. The cumulative incidence (CI) of platelet recovery to at least 20 × 109/L and 50 × 109/L without transfusion support for at least 7 days was 72.1% and 60.7%, respectively. Nineteen (86.4%) of 22 responders were able to taper off the medication; furthermore, the platelet counts remained stable 1 month after withdrawal of EPAG. Although two patients discontinued EPAG during treatment due to headache and nausea, no patients developed grade 3 or 4 toxicities. Hypoplasia of bone marrow and decreased megakaryocytes (MKs) were found to be risk factors for overall response (OR) and complete response (CR) in multivariate analysis, respectively. Overall, our results indicated that EPAG can be used in the treatment of PT and that continuous exposure to EPAG may not be necessary.

Ternary Flash Memory with a Carbazole-Based Conjugated Copolymer: WS2 Composites as Active Layers.

For nonvolatile memory devices, the design and synthesis of their substrate materials are very important. Due to the versatility and large-area fabrication of the low-temperature spin coating process, organic/inorganic nanomaterials as active layers of memory devices have been deeply studied. Inorganic nanoparticles can engage in interactions with polymers via external voltage. WS2 NPs have a large specific surface area and good conductivity. They can be used as the charge trap center in the active layer, which is conducive to the charge transfer in the active layer. Poly[2,7-9-(9-heptadecanyl)-9H-carbazole-co-benzo[4,5] imidazole[2,1-α] isoindol-11-one] (PIIO) was synthesized via the Suzuki coupling reaction. ITO/PIIO/Al and ITO/PIIO:WS2 NP/Al devices were prepared by the spin coating method and vacuum evaporation technology. All devices showed tristable switching behavior. The influence of the WS2 mass fraction on memory performance was studied. The device composite with 6 wt % WS2 NPs showed the best storage features. The OFF/ON1/ON2 current ratio was 1: 1.11 × 101: 2.03 × 104, and the threshold voltage Vth1/Vth2 was -0.60 V/-1.05 V. The device is steady for 12,000 s in three states-high-resistance state (HRS), intermediate state (IRS), and low-resistance state (LRS). After reading 3500 times, the switch-state current displayed no obvious attenuation. This work shows that the polymer and its composites have broad prospects in next-generation nonvolatile storage.

Working intentions of medical students in response to healthcare workplace violence and descending resources reform in China.

BACKGROUND: In order to curb healthcare workplace violence (WPV) and better allocate healthcare resources, China launched the descending resources reform in 2013 and tightened the anti-violence legal environment simultaneously. Medical students are expected to reconsider their working intentions of entering the medical market (inter-market effect) and choosing high- or low-level hospitals (intra-market effect) in response to the evolving WPV. The goal of this study was to explore the link between the perceived WPV incidence and medical students' willingness to practice medicine in the context of China's descending resources reform. METHOD: Medical students were selected with cluster sampling from 8 medical colleges in Zhejiang Province, China, and 1497 valid questionnaires were collected by using a five-point unbalanced scale, to perform cross-sectional empirical research using the ordered logit model (OLM). RESULTS: The perceived WPV incidence negatively correlate with the willingness of medical students to practice medicine but positively correlate with their willingness to practice in low-level hospitals, indicating the existence of inter- and intra-market effects. The anti-violence legal environment has no direct link with working intention but contributes to the perceived decline in the incidence of violence. Descending resources reform has simultaneous opposite effects on medical students, with the coexistence of prudent motives driven by reform costs and optimistic expectations of sharing external benefits. CONCLUSIONS: Safety needs and risk aversion motive play an important role in medical students' career choice when facing severe WPV. Tightening of the anti-violence legal environment and the descending resources reform could drive medical students to low-level hospitals.

Experimental study on the triaxial mechanical behaviors of the Cemented Paste Backfill: Effect of curing time, drainage conditions and curing temperature.

The application of CPB (Cemented Paste Backfill) can realize the clean, efficient, and safe mining of underground metal mines. Clear understanding on the triaxial mechanical properties of CPB is important to the CPB design and the stability analysis of the backfilled CPB structure. The triaxial mechanical properties of CPB can be significantly affected by the different curing conditions. In this research, triaxial compression tests of the CPB samples were carried out using the GCTS (Geotechnical Consulting & Testing System), and the considered curing conditions include different curing time (1, 3, 7 and 28 days), drainage conditions (drained and undrained) and curing temperatures (20 °C, 35 °C and 45 °C). The measured mechanical parameters were compared and analyzed against the framework of the Mohr-Coulomb criterion. Then, the vertical stress distribution of the backfilled CPB structure was calculated and discussed using the measured mechanical parameters. The results show that with the increase of the lateral constraint ratio (σc/Sd0), the elastoplastic stage of the measured deviator stress versus axial strain curve of CPB sample is gradually obvious. The peak deviator stress (Sdp) and the ultimate axial strain (εu) show the linear and negative exponential increase with the σc/Sd0 respectively. The number of cracks on the fractured surface of the CPB samples gradually decreased with the increase of σc/Sd0. The failure types of CPB samples were changed from tensile failure (σc/Sd0 = 0%) to the mixed tensile-shear failure (σc/Sd0≈10%) and compression-shear failure (σc/Sd0≥20%). Moreover, with the increase of curing time and curing temperature or under the drained curing condition, the peak deviator stress and cohesion (cb) of CPB can be significantly increased, but the corresponding internal friction angle (ϕb) is decreased. The shear mechanical parameters of CPB can significantly affect the vertical stress distribution inside the CPB structure. Therefore, when estimating the vertical stress distribution inside the backfilled CPB structure in engineering practices, it is necessary to focus on the changes of CPB shear parameters (cb and ϕb) caused by different curing conditions.

Colon cancer cells secreted CXCL11 via RBP-Jκ to facilitated tumour-associated macrophage-induced cancer metastasis.

Metastasis is the main cause of colon cancer-related deaths. RBP-Jκ is involved in colon cancer development, but its function in colon cancer metastasis is still unclear. Tumour-associated macrophages are the main cell components in tumour microenvironments. Here, we aimed to determine the function of RBP-Jκ in colon cancer metastasis and its underlying mechanisms for modulating interactions between colon cancer cell and tumour-associated macrophages. Through bioinformation analysis, we found that RBP-Jκ was overexpressed in colon cancer tissues and associated with advanced colon cancer phenotypes, macrophage infiltration and shorter survival overall as confirmed by our patients' data. And our patients' data show that RBP-Jκ expression and tumour-associated macrophages infiltration are associated with colon cancer metastasis and are independent prognostic factors for colon cancer patients. Tumour-associated macrophages induced colon cancer cell migration, invasion and epithelial-mesenchymal transition through secreting TGF-ß1. Colon cancer cells with high RBP-Jκ expression induced the expression of TGF-ß1 in tumour-associated macrophages by secreting CXCL11. Our research revealed that colon cancer cells secreted CXCL11 via overexpression of RBP-Jκ to enhance the expression of TGF-ß1 in tumour-associated macrophages to further promote metastasis of colon cancer cells.

Upregulation of KSRP by miR-27b attenuates schistosomiasis-induced hepatic fibrosis by targeting TGF-ß1.

Hepatic stellate cells (HSCs) are the main effectors for various types of hepatic fibrosis, including Schistosome-induced hepatic fibrosis. Multiple inflammatory cytokines/chemokines, such as transforming growth factor-ß1 (TGF-ß1), activate HSCs, and contribute to the development of hepatic fibrosis. MicroRNAs regulate gene expression at the posttranscriptional level and are involved in regulation of inflammatory cytokine/chemokine synthesis. In this study, we showed that soluble egg antigen (SEA) stimulation and Schistosoma japonicum infection downregulate miR-27b expression and increase KH-type splicing regulatory protein (KSRP) mRNA and protein levels in vitro and in vivo. miR-27b regulates the stabilization of TGF-ß1 mRNA through targeting KSRP by interacting with their AU-rich elements in hepatocytes and non-parenchymal cells, which has an effect on the activation of HSCs. Importantly, our results have shown that either knockdown miR-27b or overexpression of KSRP attenuates S. japonicum-induced hepatic fibrosis in vivo. Therefore, our study highlights the crucial role of miR-27b and KSRP in the negative regulation of immune reactions in hepatocyte and non-parenchymal cells in response to SEA stimulation and S. japonicum infection. It reveals that manipulation of miR-27b or KSRP might be a useful strategy not only for treating Schistosome-induced hepatic fibrosis but also for curing hepatic fibrosis in general.

A Long Noncoding RNA, Antisense IL-7, Promotes Inflammatory Gene Transcription through Facilitating Histone Acetylation and Switch/Sucrose Nonfermentable Chromatin Remodeling.

Long noncoding RNAs are important regulators of gene expression in innate immune responses. Antisense IL-7 (IL-7-AS) is a newly discovered long noncoding RNA in human and mouse that has been reported to regulate the expression of IL-6. However, the potential function of IL-7-AS in innate immune system is not fully understood. In this study, we found that the expression of IL-7-AS is primarily dependent on the NF-κB and MAPK signaling pathways in macrophages and intestinal epithelial cells. Functionally, IL-7-AS promotes the expression of several inflammatory genes, including CCL2, CCL5, CCL7, and IL-6, in cells in response to LPS. Specifically, IL-7-AS physically interacts with p300 to regulate histone acetylation levels around the promoter regions of these gene loci. Moreover, IL-7-AS and p300 complex modulate the assembly of SWI/SNF complex to the promoters. IL-7-AS regulates chemotaxis activity of monocytes to intestine epithelial cells with involvement of CCL2. Therefore, our data indicate a new promoting role for NF-κB/MAPK-responsive IL-7-AS in the transcriptional regulation of inflammatory genes in the innate immune system although modulation of histone acetylation around the promoters of related genes.

Self-Induced Trauma to the Genitalia: a Review of the Literature and Management Schemes.

PURPOSE OF REVIEW: Self-induced genital trauma is rare, and prompt and evidence-based early intervention can improve the urinary and sexual function of these complex patients. This review has surveyed current literature and treatment trends to evaluate the clinical approach to managing genital trauma. RECENT FINDINGS: A literature review was performed regarding self-induced genitalia trauma and trauma management between 2000 and 2019 using MEDLINE® database, the Cochrane Library® Central Search, Web of Science, and Google Scholar. In total, 42 articles were considered relevant and included in this review. Self-induced trauma can be appropriately managed with a multidisciplinary approach. Treatment goals are to preserve urinary, sexual, and reproductive function. Specific evaluation includes mechanism of injury, imaging, and determining the extent of injury and surgical repair, if indicated. Due to the rarity of these injuries and their emergent nature, much of the management is based on retrospective data. Further research is needed to improve long-term functional outcomes in trauma patients.

Mechanism by which the combination of SjCL3 and SjGAPDH protects against Schistosoma japonicum infection.

A vaccine is an important method to control schistosomiasis. Molecules related to lung-stage schistosomulum are considered potential vaccine candidates. We previously showed that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and cathepsin L3 (CL3) displayed differential expression in the lung-stage schistosomula of Schistosoma japonicum cocultured with host cells. In the present study, we prepared the two proteins and detected the protective effects of SjGAPDH by immunizing mice with this protein alone and in combination with SjCL3 with or without Freund's adjuvant. Then, we investigated the possible mechanisms underlying S. japonicum infection. The results showed that vaccination of adjuvanted SjGAPDH decreased the worm burden (37.8%) and egg load (38.1%), and the combination of adjuvanted SjGAPDH and SjCL3 further decreased the worm burden (65.6%) and egg load (70.9%) during Schistosoma japonicum infection. However, the immunization of a combination of adjuvant-free SjGAPDH and SjCL3 displayed a lower protective effect (< 15%) than those of the adjuvanted SjCL3, the adjuvanted SjGAPDH, and a combination of adjuvanted SjGAPDH and SjCL3. Flow cytometric results showed that the frequency of regulatory T cells (Tregs) was lower (P < 0.05) in the group with adjuvanted SjGAPDH and SjCL3 (2.61%) than the remaining groups. The enzyme-linked immunosorbent assay (ELISA) results indicated that except for the uninfected and infected control groups, the remaining groups displayed a Th1-type shift in immune responses. These results showed the immunization of SjGAPDH resulted in partial protection (approximately 38%); inoculation with a combination of SjCL3 and SjGAPDH in Freund's adjuvant resulted in a high immunoprotective effect (> 65%) against Schistosoma japonicum infection in mice, which was possibly caused by the reduced percentage of Tregs and a Th1-type shift in immune responses; and SjCL3 has no adjuvant-like effect, dissimilar to SmCL3.

The endocrine disruptor hexachlorobenzene can cause oxidative damage in the testis of mice.

Hexachlorobenzene is a widespread endocrine disruptor. However, the effect of hexachlorobenzene on the reproductive toxicity of male animals is not described in detail. To investigate the toxic effects of hexachlorobenzene in mouse testes, hexachlorobenzene (100, 400 and 1,600 mg/kg) is fed to mice. The morphology of the testes was analysed by haematoxylin and eosin staining. We also investigated the expression of biomarkers for oxidative stress. Database screening identified proteins that interact with hexachlorobenzene and the aryl hydrocarbon receptor, a weak ligand of hexachlorobenzene. Gene enrichment analysis and protein-protein interaction analyses were also performed. Real-time PCR detected the expression levels of the aryl hydrocarbon receptor in four different stages of testicular cells. We identified significantly increased activity levels of superoxide dismutase (p < 0.05) and catalase (p < 0.05) in mouse testes that had been subjected to oxidative damage. The cell thickness and the number of cell layers in the seminiferous tubules had decreased by varying degrees after the hexachlorobenzene treatment. Particularly, cytokines and proteins involved in transcriptional regulation showed enrichment. The highest levels of aryl hydrocarbon receptor expression were detected in the spermatocytic cell line. Hexachlorobenzene exposure caused testicular damage in mice. The toxicity characteristics of hexachlorobenzene were not dose-dependent.