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Abstract The escalating spread of drug‐resistant bacteria and viruses is a grave concern for global health. Nucleic acids dominate the drug‐resistance and transmission of pathogenic microbes. Here, imidazolium‐type poly(ionic liquid)/porphyrin (PIL‐P) based electrospun nanofibrous membrane and its cerium (IV) ion complex (PIL‐P‐Ce) are developed. The obtained PIL‐P‐Ce membrane exhibits high and stable efficiency in eradicating various microorganisms (bacteria, fungi, and viruses) and decomposing microbial antibiotic resistance genes and viral nucleic acids under light. The nuclease‐mimetic and photocatalytic mechanisms of the PIL‐P‐Ce are elucidated. Co‐infection wound models in mice with methicillin‐resistant S. aureus and hepatitis B virus demonstrate that PIL‐P‐Ce integrate the triple effects of cationic polymer, photocatalysis, and nuclease‐mimetic activities. As revealed by proteomic analysis, PIL‐P‐Ce shows minimal phototoxicity to normal tissues. Hence, PIL‐P‐Ce has potential as a “green” wound dressing to curb the spread of drug‐resistant bacteria and viruses in clinical settings.

Abstract Aims To develop a competency scale for operating room nurses and test its reliability and validity. Background The existing Chinese Registered Nurse Competency Scale and the core competency scale for operating room nurses developed abroad cannot fully meet the capacity needs of Chinese operating room nurses. Methods The scale was developed based on the results of qualitative interview and the Delphi method. Ten experts were selected for expert consultation, and 300 operating room nurses were recruited by convenience sampling for a cross‐sectional survey to test the reliability and validity of instrument.The reliability and validity of the scale was assessed based on internal consistency reliability, test–retest reliability and confirmatory factor analysis. Data collection was conducted between March to July, 2015. Results An initial scale with 42 items was confirmed, and 36 items remained. The internal consistency Cronbach's α was 0.97 for the overall scale and 0.88–0.94 for the subscales. The retest reliability ranged from 0.55–0.96. Five factors were extracted by exploratory factor analysis, and they explained 66% of the total variance. The fitting indices of the confirmatory factor analysis were as follows: χ2/df = 3.47, CFI = 0.83, TLI = 0.81, SRMR = 0.06 and RMSEA = 0.09. Conclusions The core competency scale for operating room nurses with 5 components and 36 items had acceptable reliability and validity. The scale could continue to be optimized in the future.

Abstract Background Parkinson's disease (PD) is one of the most common systemic neurodegenerative diseases and is related to the loss of dopaminergic neurons in the substantia nigra. Several studies verified that microRNA (miRNAs) targeting the Bim/Bax/caspase‐3 signaling axis is involved in the apoptosis of dopaminergic neurons in substantia nigra. In this study, we aimed to explore the role of miR‐221 in PD. Methods To examine the function of miR‐221 in vivo, we used a well‐established 6‐OHDA‐induced PD mouse model. Then we conducted adenovirus‐mediated miR‐221 overexpression in the PD mice. Results Our results showed that miR‐221 overexpression improved motor behavior of the PD mice. We demonstrated that overexpression of miR‐221 reduced the loss of dopaminergic neurons in the substantia nigra striatum by promoting their antioxidative and antiapoptosis capacities. Mechanistically, miR‐221 targets Bim, thus inhibiting Bim and Bax caspase‐3 mediated apoptosis signaling pathways. Conclusion Our findings suggest miR‐221 participates in the pathological process of PD and might be a potential drug target and provide new insight into PD treatment.

Abstract Background The participation of activating transcription factor 3 (ATF3) in transient middle cerebral artery occlusion and reperfusion injury has been reported. However, the precise mechanism of ATF3 in cerebral ischemia is little known so far. Thus, the study examines the mechanism of action underlying the protective role of ATF3 following middle cerebral artery occlusion (MCAO) in rats. Methods and results The MCAO rats exhibited reduced body weight and motor ability, while increased neurological deficits and brain infarct volume. Gene ontology (GO) enrichment and KEGG pathway analyses revealed that differentially expressed genes were mainly enriched in the TLR4/NF‐κB signaling. Moreover, ATF3 was the most differentially expressed gene in brain tissues of MCAO rats versus sham‐operated rats, which could bind to CCL2. ATF3 was reduced in MCAO rats, and ATF3 inhibited CCL2 expression to mediate the TLR4/NF‐κB signaling. Functionally, ATF3 inhibited neuronal apoptosis, microglia activation, and pro‐inflammatory cytokine production to alleviate brain injury in rats. By contrast, CCL2 was overexpressed in neurons and microglia, and CCL2 mitigated the effects of ATF3 to exacerbate brain injury in rats. Conclusion Our findings suggested that ATF3 repressed neuronal apoptosis and microglia activation caused by cerebral ischemia via targeting CCL2 and mediating the TLR4/NF‐κB signaling.

Abstract Background Simpson–Golabi–Behmel syndrome type 1 (SGBS1) is a rare X‐linked recessive disorder characterized by pre‐ and postnatal overgrowth and a broad spectrum of anomalies including craniofacial dysmorphism, heart defects, renal, and genital anomalies. Due to the ultrasound findings are not pathognomonic for this syndrome, most clinical diagnosis of SGBS1 are made postnatally. Methods A pregnant woman with abnormal prenatal sonographic findings was advised to perform molecular diagnosis. Single nucleotide polymorphism array (SNP array) was performed in the fetus, and the result was validated with multiplex ligation‐dependent probe amplification (MLPA) and real‐time quantitative PCR (qPCR). Results The prenatal sonographic presented with increased nuchal translucency at 13 gestational weeks, and later at 21 weeks with cleft lip and palate, heart defect, increased amniotic fluid index and over growth. A de novo 370Kb‐deletion covering the 5′‐UTR and exon 1 of GPC3 gene was detected in the fetus by SNP array, which was subsequently confirmed by MLPA and qPCR. Conclusion The de novo 370Kb hemizygous deletion of 5′‐UTR and exon 1 of GPC3 results in the SGBS1 of this Chinese family. Combination of ultrasound and genetics tests helped us effectively to diagnose the prenatal cases of SGBS1. Our findings also enlarge the spectrum of mutations in GPC3 gene.

Abstract Background Classical Ehlers‐Danlos syndrome (cEDS) is a heterogeneous connective tissue disorder that mainly results from the germline mutation of COL5A1 and COL5A2. The majority of the COL5A2 mutations reported to date represent structural mutations, including missense or in‐frame exon‐skipping splice mutations. The only reported synonymous mutation was expected to affect on splicing of exon 29 by prediction programs which should be further confirmed. Methods Whole exome sequencing was performed to identify the genetic variants of a Chinese boy who was characterized by skin hyperextensibility, abnormal scarring, hypermobile joints and scoliosis. Sanger sequencing was used to validate the variants in his parents. Reverse transcription polymerase chain reaction (RT‐PCR) was performed to analyze the functional effects of the variant. Results A de novo heterozygous synonymous variant (NM_000393.5:c.1977 G>A) of COL5A2 gene was identified in the patient. The results of RT‐PCR revealed that the synonymous variant led to skipping of exon 29 in the RNA transcript. Conclusions Our study supplies further supporting evidence that the synonymous COL5A2 mutation c.1977 G>A can cause skipping of exon 29 in the RNA transcript, thus resulting in the production of mutant α2(V)‐chains and clinical phenotype of cEDS. This result highlights the need to include splicing‐altering synonymous mutations into the screening for cEDS.

Abstract Background This study aimed to define the molecular basis for 12 prenatal cases of Cri‐du‐chat syndrome (CdCS) and the potential genotyping‐phenotyping association. Methods Karyotyping and single nucleotide polymorphism array analyses for copy number variants were performed. Results Nine cases had 5p terminal deletions and three had 5p interstitial deletions, and these cases had variable deletion sizes with partial overlapping. Phenotypically, besides intrauterine growth restriction (IUGR) and brain as well as heart abnormalities, hypospadias, and lung dysplasia were observed. Potential genetic causes for specific phenotypes in these cases were identified. Conclusion This study defined the molecular bases for the patients of CdCS, which is important for genetic counseling for these families. The findings of present study expand the clinical features of CdCS in the fetal period, and provided important information for further refining the genotypic–phenotypic correlations for this syndrome.

Falling weight deflectometer (FWD) is widely used in traffic transport industry. In order to solve the traceability of FWD, the definition of deflection was studied, the use and measurement of FWD was thoroughly analysed, and the measurement parameters were determined. Calibration device, standard foundation, and experimental environmental conditions of FWD was set up. The measurement uncertainty of the calibration equipment has been analysed. Through the test of the typical FWD, the performance of the calibration equipment is tested. Through the establishment of the traceability chain of ‘ Absolute normal low frequency vibration standard device-FWD calibration equipment-FWD’, it can meet the calibration/verification requirements of FWD.

The reaction-diffusion equations have been widely used in physics, chemistry, and other areas. Forest fire can also be described by such equations. We here propose a fighting forest fire model. By using the normal form approach theory and center manifold theory, we analyze the stability of the trivial solution and Hopf bifurcation of this model. Finally, we give the numerical simulations to illustrate the effectiveness of our results.

Background and Purpose: Restless legs syndrome (RLS) has been suggested as a prodromal symptom of Parkinson disease (PD). Olfactory or taste dysfunction can also occur preceding PD diagnosis. However, whether RLS is associated with chemosensory dysfunction remains unknown. We thus aim to investigate the association between RLS and perceived olfactory and taste dysfunction., Methods: We performed a cross-sectional analysis including 90,337 Chinese adults free of neurodegenerative diseases in the Kailuan study in 2016. Presence of RLS was defined using revised RLS diagnostic criteria or the Cambridge-Hopkins questionnaire for RLS. Perceived olfactory and taste dysfunction was collected via a questionnaire. The association between RLS and perceived olfactory and taste dysfunction was assessed using logistic regression model, adjusting for potential cofounders such as age, sex, and medical history., Results: RLS was associated with high odds of having perceived olfactory and/or taste dysfunction (adjusted odds ratio = 5.92, 95% confidence interval = 3.11-11.3). The significant association persisted when using the Cambridge-Hopkins questionnaire (adjusted odds ratio = 5.55, 95% confidence interval = 2.37-13.0) or when excluding participants with major chronic diseases., Conclusions: RLS was associated with increased odds of perceived olfactory and taste dysfunction., (© 2021 European Academy of Neurology.)

The tumor suppressor p53 plays essential roles in cellular protection mechanisms against a variety of stress stimuli and its activation induces apoptosis or autophagy in certain cancer cells. Here, we identified protopine, an isoquinoline alkaloid isolated from Nandina domestica, as an activator of the p53 pathway from cell-based natural compound screening based on p53-responsive transcription. Protopine increased the p53-mediated transcriptional activity and promoted p53 phosphorylation at the Ser15 residue, resulting in stabilization of p53 protein. Moreover, protopine up-regulated the expression of p21 WAF1/CIP1 and BAX, downstream genes of p53, and inhibited the proliferation of HCT116 colon cancer cells. Apoptosis was elicited by protopine as indicated by caspase-3/7 activation, poly ADP ribose polymerase cleavage, and increased population of Annexin V-FITC-positive cells. Furthermore, protopine induced the formation of microtubule-associated protein 1 light chain 3 (LC3) puncta and LC3-II turnover, typical biochemical markers of autophagy, in HCT116 cells. Our findings suggest that protopine exerts its antiproliferative activity by stimulating the p53 pathway and may have potential as a chemopreventive agent for human colon cancer., (© 2019 John Wiley & Sons, Ltd.)

Background and Purpose: The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor (PDGF) are important steps in cardiovascular diseases, including neointimal lesion formation, myocardial infarction and atherosclerosis. Here, we evaluated the rubiarbonone C-mediated signalling pathways that regulate PDGF-induced VSMC proliferation and migration., Experimental Approach: Cell proliferation and migration were measured in cells treated with rubiarbonone C followed by PDGF BB using the MTT assay, [ 3 H]-thymidine incorporation, flow cytometry and wound-healing migration assay, MMP gelatin zymography, a fluorescence assay for F-actin. Western blotting of molecules including MAPK, focal adhesion kinase (FAK) and STAT3 and an immunofluorescence assay using anti-PCNA and -STAT3 antibodies were performed to evaluate rubiarbonone C signalling pathway(s). The medial thickness of the carotid artery was evaluated using a mouse carotid ligation model., Key Results: Rubiarbonone C inhibited PDGF-induced VSMC proliferation and migration and diminished the ligation-induced increase in medial thickness of the carotid artery. In PDGF-stimulated VSMCs rubiarbonone C decreased the following: (i) levels of cyclin-dependent kinases, cyclins, PCNA and hyperphosphorylated retinoblastoma protein; (ii) levels and activity of MMP2 and MMP9; (iii) activation of MAPK; (iv) F-actin reorganization, by reducing FAK activation; (v) activation of STAT3., Conclusions and Implications: These findings suggest that rubiarbonone C inhibits the proliferation and migration of VSMCs by inhibiting the FAK, MAPK and STAT3 signalling pathways. Therefore, rubiarbonone C could be a good candidate for the treatment of cardiovascular disease., (© 2017 The British Pharmacological Society.)

Paeonia suffruticosa has been traditionally employed for vitalizing blood circulation and alleviating liver and inflammatory diseases. The pathways by which palbinone (PB) isolated from P. suffruticosa mediates heme oxygenase-1 (HO-1) induction were investigated using the specific inhibitors for PI3K and mitogen activated protein kinases pathways. The effect of PB-treatment on Nrf2 translocalization and HO-1-antioxidant response element (ARE) regulation was examined employing Western blot and luciferase assays. PB induced HO-1 expression via the activation of Nrf2 in the hepatic cells, and ARE-dependent genes were stimulated via the PB-mediated Nrf2 activation. PB-mediated HO-1 expression could be involved with PI3K/Akt and ERK1/2 pathways. Our study suggests the mechanism by which PB induces HO-1 expression in the hepatic cells. This might substantiate the traditional applications of P. suffruticosa for the treatment of oxidative stress-related diseases including oxidant and inflammatory-mediated vascular and liver diseases., (Copyright © 2013 John Wiley & Sons, Ltd.)

The stem and root barks of Ulmus davidiana var. japonica (Ulmaceae) have been used to treat inflammatory diseases including mastitis, rhinitis, sinusitis, and enteritis. In an ongoing study focused on the discovery of natural anti-inflammatory compounds from natural products, a methanol extract of the stem and root barks of U. davidiana var. japonica showed anti-inflammatory activities. Activity-guided fractionation of the methanol extract yielded a new trihydroxy fatty acid, 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1), and a known compound, pinellic acid (2). These two trihydroxy fatty acids 1 and 2 inhibited prostaglandin D₂ production with IC₅₀ values of 25.8 and 40.8 μM, respectively. These results suggest that 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1) and pinellic acid (2) are among the anti-inflammatory principles in this medicinal plant., (Copyright © 2012 John Wiley & Sons, Ltd.)

Ganoderma lucidum is known as a medicinal mushroom used in traditional medicine. In our study, the cytotoxic activities of 17 compounds (1-17) isolated from the fruiting bodies of G. lucidum were investigated. Among them, ergosta-7,22-diene-2β,3α,9α-triol (EGDT) induced apoptosis in HL-60 human premyelocytic leukemia cells. EGDT activated the apoptotic process, including DNA fragmentation and caspase-3 activity. In immunoblotting analysis, treatment with EGDT resulted in the cleavage of procaspase-3 and poly(ADP-ribose) polymerase (PARP) into active forms. In the in vivo study, the administration (i.p.) of EGDT to Lewis lung carcinoma (LLC)-inoculated mice evidenced a significant inhibition of tumor growth. These results indicate that EGDT was one of the apoptotic constituents of G. lucidum, and might be an antitumor agent., (Copyright © 2011 John Wiley & Sons, Ltd.)

During the screening effort to discover new types of protein tyrosine phosphatase 1B (PTP1B) inhibitors, it was found that a MeOH extract of the leaves and stems of Weigela subsessilis (Caprifoliaceae) inhibited the enzyme activity. By means of an in vitro bioassay-guided fractionation on the MeOH extract, two 24-norursane triterpenes, ilekudinol A (1) and ilekudinol B (2), were isolated as active metabolites. Compounds 1 and 2 inhibited PTP1B with IC(50) values of 29.1 ± 2.8 and 5.3 ± 0.5 μM, respectively. Kinetic studies suggest that both 1 and 2 are non-competitive inhibitors of PTP1B. The findings indicate that the free carboxyl group at C-28 in this type of triterpenes plays a critical role in the inhibition of PTP1B., (Copyright © 2010 John Wiley & Sons, Ltd.)

Inhibition of fatty acid synthase (FAS) has been proposed to be a new therapeutic target for the treatment of cancer and obesity. In our preliminary screening study on the FAS inhibitory activity, a n-hexane soluble fraction prepared from the fruit of Schisandra chinensis (Schisandraceae) was found to inhibit FAS activity at 100 microg/mL. Nine dibenzocyclooctadiene lignans were isolated from the active fraction and were evaluated for their inhibitory effect on FAS for the first time. The compounds possessing a benzoyl or tigloyl group in the dibenzocyclooctadiene skeleton entirely inhibited the FAS activity in a dose dependent manner. The findings may be partially related to the anticancer effect of the medicinal plant, suggesting a further study on the anticancer potential of dibenzocyclooctadiene derivatives.

Gardeniae Fructus is a traditional medicine used for the treatment of contusion such as ankle sprain. Geniposide is one of the main components of Gardeniae Fructus with diverse biological activities. In order to gain further insight into the therapeutic action of Gardeniae Fructus extract (GFE) and geniposide on ligament injuries, a new in vitro model was developed in the present study. Rat hind ankle ligament fibroblasts (RHALFs) derived from Sprague-Dawley rats were cultured, and the cell proliferation and collagen content were examined by MTT and a Sirius Red-based colorimetric assay after stimulating with each drug. The cell growth of RHALFs was promoted by culturing with 37.5-150 microg/mL of GFE and 25-200 microM of geniposide. The content of collagen in the RHALFs was significantly increased up to 131.4% and 124.2% of the control value by culturing with the GFE and geniposide, respectively. By contrast, both cell growth and collagen content were impaired by adding 25-200 microM of diclofenac, one of the common medications for ligament injuries. The findings suggest that GFE and geniposide may ameliorate the treatment of ligament injuries by proliferating ligament fibroblasts and promoting the synthesis of collagen. However, the use of diclofenac to treat acute ligament injuries should be reassessed although it possesses a potential effect on relieving symptoms.

Five pentacyclic triterpenoids (1-5) and a sterol (6) were isolated from the stem-bark of Styrax japonica. The six compounds, 1-6, were determined to be 3beta-acetoxy-28-hydroxyolean-12-ene (1), 3beta-acetoxyolean-12-en-28-acid (2), 3beta-acetoxyolean-12-en-28-aldehyde (3), 3beta-acetoxy-17beta-hydroxy-28-norolean-12-ene (4), taraxerol (5) and stigmasterol (6), respectively, by spectroscopic means, including the 2D-NMR technique. Compound 4 is a newly discovered natural compound. The protein tyrosine phosphatase 1B (PTP1B) inhibitory activities of the isolated compounds (1-6) were determined in vitro. Among the isolated compounds, 3beta-acetoxyolean-12-en-28-acid (2) and 3beta-acetoxyolean-12-en-28-aldehyde (3) had the most potent inhibitory PTP1B activity, with IC50 values of 7.8 and 9.3 microm, respectively., ((c) 2008 John Wiley & Sons, Ltd.)

The EtOH extract from the rhizomes of Astilbe chinensis (Saxifragaceae) exhibited potent antioxidant activity in preliminary screening. Since oxidative stress is known to be involved in the inflammatory response after UVB exposure, the ability of an A. chinensis extract to inhibit UVB-induced PGE2 and NO production was examined. UVB irradiation (35 mJ/cm2) increased PGE2 and NO production, which were significantly decreased by pre-administration of the extract in a dose-dependent manner. The A. chinensis extract also preserved the cellular antioxidant capacity after UVB irradiation, which was determined by the GSH content. UVB irradiation enhanced the formation of ROS in the keratinocytes, which was determined using DCFH-DA, a redox sensitive dye. The levels of intracellular ROS were also significantly reduced by pre-treatment of the extract in a dose-dependent manner measured 9 h after UVB irradiation. The results suggest that the A. chinensis extract may have a protective effect on the UVB-injured keratinocytes by inhibiting PGE2 and NO production, possibly through the inhibition of intracellular ROS accumulation., (2004 John Wiley & Sons, Ltd.)

The ethanol extract from the fruit of Terminalia chebula (Combretaceae) exhibited significant inhibitory activity on oxidative stress and the age-dependent shortening of the telomeric DNA length. In the peroxidation model using t-BuOOH, the T. chebula extract showed a notable cytoprotective effect on the HEK-N/F cells with 60.5 +/- 3.8% at a concentration of 50 microg/ml. In addition, the T. chebula extract exhibited a significant cytoprotective effect against UVB-induced oxidative damage. The life-span of the HEK-N/F cells was elongated by 40% as a result of the continuous administration of 3 microg/ml of the T. chebula extract compared to that of the control. These observations were attributed to the inhibitory effect of the T. chebula extract on the age-dependent shortening of the telomere, length as shown by the Southern blots of the terminal restriction fragments (TRFs) of DNA extracted from subculture passages., (Copyright (c) 2004 John Wiley & Sons, Ltd.)