Application of Four-Dimensional Pelvic Floor Ultrasound in the Diagnosis of Postpartum Pelvic Floor Dysfunction and Evaluation of Curative Effect.

Objective: To explore the application of four-dimensional pelvic floor ultrasound in the diagnosis of postpartum pelvic floor dysfunction (PFD) and evaluation of curative effect. Methods: A total of 100 patients with postpartum PFD undergoing vaginal delivery in the hospital were enrolled as the research objects between January 2020 and January 2023. A total of 100 postpartum women with good pelvic floor muscle function during the same period were enrolled as a control group. Both groups underwent four-dimensional pelvic floor ultrasound detection. The bladder neck descent (BND), retrovesical angle (RVA), urethral tilt angle (UTA), urethral rotation angle (ROT), levator ani thickness under rest state (LATr), levator ani thickness under Valsalva state (LATs), levator ani hiatus area under rest state (LHAr) and levator ani hiatus area under Valsalva state (LHAs) in both groups were compared. The patients in the study group were given Kegel training for pelvic floor muscle rehabilitation exercise and bio-feedback electrical stimulation. According to the clinical curative effect, patients in the study group were divided into a recovery group (n=87) and a non-recovery group (n=13). The value of four-dimensional pelvic floor ultrasound in the diagnosis of PFD and evaluation of curative effect was analyzed. Results: In the observation group, BND, RVA, UTA, ROT, LHAr, and LHAs were higher, while LATr and LATs were lower compared to the control group. (P < .05). The results of ROC curves analysis showed that the AUC of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs in the diagnosis of PFD was 0.818, greater than that of the single index (0.728, 0.705, 0.680, 0.715, 0.677, 0.696, 0.719, 0.654; P < .05). BND, RVA, UTA, ROT, LHAr, and LHAs in the non-recovery group were higher than those in the recovery group, while LATr and LATs were lower than those in the recovery group (P < .05). The results of ROC curves analysis showed that the Area Under the Curve (AUC）of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs for predicting the curative effect were 0.804, greater than that of a single index (0.725, 0.653, 0.651, 0.744, 0.733, 0.720, 0.661, 0.718; P < .05). Conclusion: Four-dimensional pelvic floor ultrasound can be applied to intuitively evaluate the structure and function of postpartum pelvic floor tissues, which can provide a reliable basis for the diagnosis of postpartum PFD and evaluation of curative effect.

Sirt6 protects cardiomyocytes against doxorubicin-induced cardiotoxicity by inhibiting P53/Fas-dependent cell death and augmenting endogenous antioxidant defense mechanisms.

Sirt6, a class III NAD+-dependent deacetylase of the sirtuin family, is a highly specific H3 deacetylase and plays important roles in regulating cellular growth and death. The induction of oxidative stress and death is the critical mechanism involved in cardiomyocyte injury and cardiac dysfunction in doxorubicin-induced cardiotoxicity, but the regulatory role of Sirt6 in the fate of DOX-impaired cardiomyocytes is poorly understood. In the present study, we exposed Sirt6 heterozygous (Sirt6+/-) mice and their littermates as well as cultured neonatal rat cardiomyocytes to DOX, then investigated the role of Sirt6 in mitigating oxidative stress and cardiac injury in the DOX-treated myocardium. Sirt6 partial knockout or silencing worsened cardiac damage, remodeling, and oxidative stress injury in mice or cultured cardiomyocytes with DOX challenge. Cardiomyocytes infected with adenoviral constructs encoding Sirt6 showed reversal of this DOX-induced damage. Intriguingly, Sirt6 reduced oxidative stress injury by upregulating endogenous antioxidant levels, interacted with oxidative stress-stirred p53, and acted as a co-repressor of p53 in nuclei. Sirt6 was recruited by p53 to the promoter regions of the target genes Fas and FasL and further suppressed p53 transcription activity by reducing histone acetylation. Sirt6 inhibited Fas/FasL signaling and attenuated both Fas-FADD-caspase-8 apoptotic and Fas-RIP3 necrotic pathways. These results indicate that Sirt6 protects the heart against DOX-induced cardiotoxicity by upregulating endogenous antioxidants, as well as suppressing oxidative stress and cell death signaling pathways dependent on ROS-stirred p53 transcriptional activation, thus reducing Fas-FasL-mediated apoptosis and necrosis. •Sirt6 is significantly decreased in DOX-insulted mouse hearts and cardiomyocytes. •Sirt6 attenuates DOX-induced cardiac atrophy, dysfunction and oxidative stress. • Sirt6 reduces oxidative stress injury by upregulating endogenous antioxidants. • Sirt6 interacts with p53 as a co-repressor to suppress p53 transcriptional regulation and inhibits Fas-FasL-mediated apoptosis and necrosis downstream of p53.

Effects of Ferroptosis on Cardiovascular Diseases.

Ferroptosis is a novel form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which causes membrane injury. Under the catalysis of iron ions, cells deficient in glutathione peroxidase (GPX4) cannot preserve the balance in lipid oxidative metabolism, and the buildup of reactive oxygen species on the membrane lipids leads to cell death. An increasing body of evidence suggests that ferroptosis plays a significant role in the development and occurrence of cardiovascular diseases. In this paper, we mainly elaborated on the molecular mechanisms regulating ferroptosis and its impact on cardiovascular disease to lay the groundwork for future studies on the prophylaxis and treatment of this patient population.

The effectiveness of a workplace violence prevention strategy based on situational prevention theory for nurses in managing violent situations: a quasi-experimental study.

BACKGROUND: Workplace violence (WPV) poses a significant occupational hazard for nurses. The efficacy of current education and training programs in mitigating WPV incidence among nurses remains uncertain, possibly due to insufficient consideration of clinical contexts and nurses' specific needs. Therefore, this study developed a WPV prevention strategy based on the actual requirements of clinical nurses and situational prevention theory and aimed to explore its application effects. METHODS: Under the guidance of situational prevention theory, a WPV prevention strategy for nurses was constructed through literature review, semi-structured interviews and focus group discussion. This study adopted a self-controlled research design, and trained 130 nurses selected from a comprehensive tertiary grade A hospital in Suzhou in this WPV prevention strategy. Data were collected through structured questionnaires, including the revised WPV questionnaire, WPV severity grading scale, and hospital WPV coping resources scale. The WPV incidence, severity, and WPV coping resource scores of nurses were collected before the intervention, as well as at 3 months, 6 months, and 9 months after training. RESULTS: The WPV prevention strategy comprised 11 prevention plans based on 11 high-risk situational elements of WPV. Each prevention plan included the WPV prevention flowchart, treatment principle, and communication strategy. The strategy demonstrated excellent feasibility and practicality. Following the intervention, the overall incidence of WPV among nurses significantly decreased from 63.85% (baseline) to 46.15% (9 months after training) (P < 0.05). After the training, the severity of psychological violence (Wald χ² = 20.066, P < 0.001) and physical violence (Wald χ² = 9.100, P = 0.028) reported by nurses decreased compared to the baseline (P < 0.05). Moreover, the overall WPV coping resource score significantly increased from [66.50 (57.00, 77.25) points] (baseline) to [80.00 (68.00, 97.25) points] (9 months after training) (P < 0.05). CONCLUSIONS: The described WPV prevention strategy, grounded in situational prevention theory and tailored to the needs of clinical nurses, effectively reduced WPV incidence, mitigated its severity, and enhanced nurses' WPV coping resources. This approach offered new avenues for nurses in the prevention of WPV.

[Frontiers and development in live-cell super-resolution fluorescence microscopy].

This paper reviews the research progress on live-cell super-resolution fluorescence microscopy, discusses the current research status and hotspots in this field, and summarizes the technological application of super-resolution fluorescence microscopy for live-cell imaging. To date, this field has gained progress in numerous aspects. Specifically, the structured illumination microscopy, stimulated emission depletion microscopy, and the recently introduced minimal photon fluxes microscopy are the current research hotspots. According to the current progress in this field, future development trend is likely to be largely driven by artificial intelligence as well as advances in fluorescent probes and relevant labelling methods.

NMDA receptor antagonists engender neuroprotection against gp120-induced cognitive dysfunction in rats through modulation of PKR activation, oxidative stress, ER stress and IRE1α signal pathway.

It is widely accepted that the surface glycoprotein (gp120) of human immunodeficiency virus-1 (HIV-1) plays an important role in HIV-1-induced nerve damage and pathogenesis of HIV-associated neurocognitive disorders (HAND). Our previous work has demonstrated that gp120 enhanced excitatory postsynaptic currents (EPSCs) mediated by N-methyl-d-aspartate receptors (NMDARs) and caused neural injury. However, the relationship between gp120, NMDARs and HAND is still unclear. Several lines of evidence indicate that double-stranded RNA-activated protein kinase (PKR) is involved in NMDA-induced cerebral ischaemia and retinal damage, but because its role in neuropathology is still debated, we examined whether PKR links oxidative stress and endoplasmic reticulum (ER) stress to exert a deleterious role in the rat model with gp120-induced dementia. In this study, we found that NMDAR antagonist memantine or PKR inhibitor C16 improved gp120-induced learning and memory impairment and inhibited gp120-induced PKR activity. Furthermore, memantine or C16 was found to attenuate gp120-induced neuroinflammation, oxidative stress, ER stress and its downstream IRE1α/JNK pathway. Additionally, memantine or C16 evidently inhibited apoptotic pathways by reducing the Bax and caspase-3, -8, -9 expressions and increasing Bcl-2 expression. So the NMDA receptor antagonists could alleviate HIV/gp120-induced dementia in the rat model by altering PKR level. In conclusion, this study demonstrates that NMDARs play a key role in HIV/gp120-induced hippocampal damage and cognitive dysfunction through PKR-mediated oxidative stress, ER stress, and IRE1α/JNK signalling pathway in rats, and implicating PKR inhibitors could provide a novel neuroprotective strategy for HAND via inhibiting ER stress and its downstream IRE1α signalling pathway.

Oxygen Self-Supply Engineering-Ferritin for the Relief of Hypoxia in Tumors and the Enhancement of Photodynamic Therapy Efficacy.

Hypoxia is a hallmark of the tumor microenvironment (TME) that promotes tumor development and metastasis. Photodynamic therapy (PDT) is a promising strategy in the treatment of tumors, but it is limited by the lack of oxygen in TME. In this work, an O2 self-supply PDT system is constructed by co-encapsulation of chlorin e6 (Ce6) and a MnO2 core in an engineered ferritin (Ftn), generating a nanozyme promoted PDT nanoformula (Ce6/Ftn@MnO2 ) for tumor therapy. Ce6/Ftn@MnO2 exhibits a uniform small size (15.5 nm) and high stability due to the inherent structure of Ftn. The fluorescence imaging and immunofluorescence analysis demonstrate the pronounced accumulation of Ce6/Ftn@MnO2 in the tumors of mice, and the treatment significantly decreases the expression of hypoxia-inducible factor (HIF)-1α. The Ce6/Ftn@MnO2 nanoplatform exerts a more potent anti-tumor efficacy with negligible damage to normal tissues compared to the treatment with free Ce6. Moreover, the weak acidity and the presence of H2 O2 in TME significantly enhances the r1 relativity of Ce6/Ftn@MnO2 , resulting in a prominent enhancement of MRI imaging in the tumor. This bio-mimic Ftn strategy not only improves the in vivo distribution and retention of Ce6, but also enhances the effectiveness and precision of PDT by TME modulation.

Cadmium induces placental glucocorticoid barrier damage by suppressing the cAMP/PKA/Sp1 pathway and the protective role of taurine.

Cadmium (Cd) exposure during pregnancy damages the placental glucocorticoid (GC) barrier, exposes the foetus to excess corticosterone (CORT) levels, and eventually inhibits foetal development. In addition, taurine (Tau) alleviates the toxicity of Cd on liver and kidney, but limited data are available on the role of Tau against the toxicity of heavy metals on female reproduction and fetal development. The present study was conducted to investigate the specific mechanism of Cd-induced placental GC barrier damage and the protective role of Tau. Pregnant rats were administered CdCl2 (1 mg/kg/day) and Tau (100, 200, or 300 mg/kg/day) by gavage from gestational day (GD) 0 to 19. The data showed that CdCl2 increased the foetal growth restriction (FGR) rate of the offspring, and the levels of CORT in the placental, maternal and foetal serum. Treatment with Tau significantly reversed the impact of Cd on both maternal and fetal parameters. Additionally, Tau can attenuate Cd-induced inhibition of 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2) and specificity protein 1 (Sp1) in vivo and vitro. Furthermore, Sp1-siRNA alone reduced 11ß-HSD2 levels and had a further inhibitory effect when the cells were treated with Cd simultaneously. Moreover, Cd suppressed cAMP/PKA signalling. Forskolin (adenylate cyclase agonist) pretreatment activated cAMP/PKA signalling and restored the Cd-induced downregulation of Sp1 and 11ß-HSD2. Tau alleviated the Cd-induced decrease of Sp1 via activating cAMP/PKA signalling. Therefore, the results highlight that Tau protects against Cd-induced impairments in GC barrier damage by upregulating the cAMP/PKA/Sp1 pathway in placental trophoblasts.

Electrochemical Tip-Enhanced Raman Spectroscopy: An In Situ Nanospectroscopy for Electrochemistry.

Revealing the intrinsic relationships between the structure, properties, and performance of the electrochemical interface is a long-term goal in the electrochemistry and surface science communities because it could facilitate the rational design of electrochemical devices. Achieving this goal requires in situ characterization techniques that provide rich chemical information and high spatial resolution. Electrochemical tip-enhanced Raman spectroscopy (EC-TERS), which provides molecular fingerprint information with nanometer-scale spatial resolution, is a promising technique for achieving this goal. Since the first demonstration of this technique in 2015, EC-TERS has been developed for characterizing various electrochemical processes at the nanoscale and molecular level. Here, we review the development of EC-TERS over the past 5 years. We discuss progress in addressing the technical challenges, including optimizing the EC-TERS setup and solving tip-related issues, and provide experimental guidelines. We also survey the important applications of EC-TERS for probing molecular protonation, molecular adsorption, electrochemical reactions, and photoelectrochemical reactions. Finally, we discuss the opportunities and challenges in the future development of this young technique.

Saikosaponin D Alleviates DOX-induced Cardiac Injury In Vivo and In Vitro.

ABSTRACT: As a highly efficient anticancer agent, doxorubicin (DOX) is used for treatment of various cancers, but DOX-induced oxidative damages contribute to a degenerative irreversible cardiac toxicity. Saikosaponin D (SSD), which is a triterpenoid saponin with many biological activities including anti-inflammatory effects and antioxidant properties, provides protection against pathologic cardiac remodeling and fibrosis. In the present study, we investigated the work of SSD for DOX-induced cardiotoxicity and the involved mechanisms. We observed that DOX injection induced cardiac injury and malfunction and decreased survival rate. Besides, DOX treatment increased lactate dehydrogenase leakage, cardiomyocyte apoptosis, and myocardium fibrosis and decreased the size of cardiomyocytes. Meanwhile, all the effects were notably attenuated by SSD treatment. In vitro, we found that 1 µM SSD could enhance the proliferation of H9c2 cells and inhibit DOX-induced apoptosis. It was found that the levels of malondialdehyde (MDA) and reactive oxygen species were significantly reduced by improving the activities of the endogenous antioxidative enzymes including catalase and glutathione peroxidase. Furthermore, SSD treatment could downregulate the DOX-induced p38 phosphorylation. Our results suggested that SSD efficiently protected the cardiomyocytes from DOX-induced cardiotoxicity by inhibiting the excessive oxidative stress via p38-MAPK (mitogen-activated protein kinase, MAPK) signaling pathway.

UVA-LED-Assisted Activation of the Ferrate(VI) Process for Enhanced Micropollutant Degradation: Important Role of Ferrate(IV) and Ferrate(V).

This paper investigated ultraviolet A light-emitting diode (UVA-LED) irradiation to activate Fe(VI) for the degradation of micropollutants (e.g., sulfamethoxazole (SMX), enrofloxacin, and trimethoprim). UVA-LED/Fe(VI) could significantly promote the degradation of micropollutants, with rates that were 2.6-7.2-fold faster than for Fe(VI) alone. Comparatively, UVA-LED alone hardly degraded selected micropollutants. The degradation performance was further evaluated in SMX degradation via different wavelengths (365-405 nm), light intensity, and pH. Increased wavelengths led to linearly decreased SMX degradation rates because Fe(VI) has a lower molar absorption coefficient at higher wavelengths. Higher light intensity caused faster SMX degradation, owing to the enhanced level of reactive species by stronger photolysis of Fe(VI). Significantly, SMX degradation was gradually suppressed from pH 7.0 to 9.0 due to the changing speciation of Fe(VI). Scavenging and probing experiments for identifying oxidative species indicated that high-valent iron species (Fe(V)/Fe(IV)) were responsible for the enhanced degradation. A kinetic model involving target compound (TC) degradation by Fe(VI), Fe(V), and Fe(IV) was employed to fit the TC degradation kinetics by UVA-LED/Fe(VI). The fitted results revealed that Fe(IV) and Fe(V) primarily contributed to TC degradation in this system. In addition, transformation products of SMX degradation by Fe(VI) and UVA-LED/Fe(VI) were identified and the possible pathways included hydroxylation, self-coupling, bond cleavage, and oxidation reactions. Removal of SMX in real water also showed remarkable promotion by UVA-LED/Fe(VI). Overall, these findings could shed light on the understanding and application of UVA-LED/Fe(VI) for eliminating micropollutants in water treatments.

Enhanced Permanganate Activation under UVA-LED Irradiation: Unraveled Mechanism Involving Manganese Species and Hydroxyl Radical.

Permanganate [Mn(VII)] has gained broad attention in water treatment. However, its limited reactivity toward some refractory micropollutants hinders its application for micropollutant degradation. Herein, we introduced UVA-LED photolysis of Mn(VII) (UVA-LED/Mn(VII)) to degrade micropollutants (diclofenac (DCF), 4-chlorophenol (4-CP), atrazine, and nitrobenzene) by selecting DCF and 4-CP as target micropollutants. The effects of operating conditions (e.g., light intensity, radiation wavelengths, pH, and water constituents) on DCF and 4-CP degradation as well as the underlying mechanisms were systematically studied. The degradation rates of DCF and 4-CP linearly decreased with increasing radiation wavelengths (from 365 to 405 nm), likely due to the decreased molar absorption coefficients and quantum yields of Mn(VII). Reactive manganese species (RMnS), including Mn(V), Mn(III), and HO•, were generated in the UVA-LED/Mn(VII) process. Mn(V) and HO• were responsible for DCF degradation, while Mn(III), HO•, and likely Mn(V) accounted for 4-CP degradation. Competitive kinetic results revealed that contributions of RMnS and HO• decreased with increasing radiation wavelengths, wherein RMnS played the dominant role. Increasing pH displayed opposite effects on DCF and 4-CP degradation with higher degradation efficiency obtained at acidic pH for the former one but alkaline pH for the latter one. The presence of water background ions (e.g., Cl-, HCO3-, and Ca2+) barely influenced DCF and 4-CP degradation. Finally, in comparison with Mn(VII) alone, enhanced degradation of DCF and 4-CP by UVA-LED/Mn(VII) was observed in real waters. This work advances the understanding of the photochemistry of manganese species in micropollutant degradation and facilitates Mn(VII) oxidation in practical application.

Selenium attenuates the cadmium-induced placenta glucocorticoid barrier damage by up-regulating the expression of specificity protein 1.

Cadmium (Cd) is an environmental pollutant and pregnant women are especially susceptible to the effects of exposure to Cd. Our previous study found Cd can be accumulated in the placenta and causes fetal growth restriction (FGR) through damage the placental glucocorticoid barrier. Selenium (Se), as an essential micronutrient, can allivate Cd-induced toxicity. In this study, we aim to explore the protective mechanism of Se against Cd-induced the placental glucocorticoid barrier damage and FGR. Pregnant Sprague Dawley (SD) rats were exposed to CdCl2 (1 mg/kg/day) and Na2 SeO3 (0.1-0.2-0.3 mg/kg/day) by gavage from gestational day (GD) 0 to GD 19. The results showed that reduced fetal weight, increased corticosterone concentrations in the maternal and fetal serum, and impaired placental labyrinth layer blood vessel development, appeared in pregnant rats after Cd exposure and improved after treated with Se. In cell experiments, we confirmed that Se reduces Cd-induced apoptosis. Moreover, Se can abolish Cd-induced 11ß-HSD2 and specificity protein 1 (Sp1) decreasing in vivo and vitro. In human JEG-3 cells, the knockdown of Sp1 expression by small interfering RNA can suppressed the protective effect of Se on Cd-induced 11ß-HSD2 decreasing. In general, our results demonstrated that Se is resistant to Cd-induced FGR through upregulating the placenta barrier via activation of the transcription factor Sp1.

Decoupled Redox Catalytic Hydrogen Production with a Robust Electrolyte-Borne Electron and Proton Carrier.

Electrolytic water splitting is an effective approach for H2 mass production. A conventional water electrolyzer concurrently generates H2 and O2 in neighboring electrode compartments separated by a membrane, which brings about compromised purity, energy efficiency, and system durability. On the basis of distinct redox electrochemistry, here, we report a system that enables the decoupling of both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) from the electrodes to two spatially separated catalyst bed reactors in alkaline solutions. Through a pair of close-loop electrochemical-chemical cycles, the system operates upon 7,8-dihydroxy-2-phenazinesulfonic acid (DHPS) and ferricyanide-mediated HER and OER, respectively, on Pt/Ni(OH)2 and NiFe(OH)2 catalysts. Near unity faradaic efficiency and sustained production of hydrogen has been demonstrated at a current density up to 100 mA/cm2. The superior reaction kinetics, particularly the HER reaction mechanism of DHPS as a robust electrolyte-borne electron and proton carriers, were scrutinized both computationally and experimentally. We anticipate the system demonstrated here would provide an intriguing alternative to the conventional water electrolytic hydrogen production.

Efficient Degradation of Organoarsenic by UV/Chlorine Treatment: Kinetics, Mechanism, Enhanced Arsenic Removal, and Cytotoxicity.

Roxarsone (ROX) has been widely used as an organoarsenic additive in animal feeding operations and poses a risk to the environment. Here, we first report the efficient degradation of ROX by UV/chlorine, where the kinetics, removal of total arsenic (As), and cytotoxicity were investigated. The kinetics study presented that reactive chlorine species (RCS) and HO• were the dominant species to react with ROX. Furthermore, the degradation rate of ROX can reach the maximum value at pH 7.5 due to the formation of more RCS. The degradation of ROX was affected by the amount of chlorine, pH, and water matrix. Through product analysis and Gauss theoretical calculation, two possible ROX degradation pathways were proposed. The free radicals attacked the As-C bond of ROX and resulted in releasing arsenate (As(V)). It was the reason that for an enhancement of the removal of total As by ferrous appeared after UV/chlorine, and over 98% of the total As was removed. In addition, cytotoxicity studies indicated that the cytotoxicity significantly enhanced during the degradation of ROX by UV/chlorine. However, by combination of UV/chlorine and adsorption, cytotoxicity can be greatly eliminated, probably due to the removal of As(V) and chlorinated products. These results further demonstrated that UV/chlorine treatment could be an effective method for the control of the potential environmental risks posed by organoarsenic.

Trajectories of the current situation and characteristics of workplace violence among nurses: a nine-year follow-up study.

BACKGROUND: Workplace violence (WPV) among nurses has become an increasingly serious public health issue worldwide. Investigating the status quo and characteristics of WPV among nurses in different time periods can help hospital managers understand the current status of WPV and its trends over time. This study aimed to understand the current situation of WPV among nurses in Suzhou general hospitals from 2010 to 2019 and analyze changes over time. METHODS: A cross-sectional study was conducted to investigate 942, 2,110 and 2,566 nurses in 6 fixed polyclinic hospitals in Suzhou in 2010, 2015 and 2019, respectively. This study used the revised version of the hospital WPV questionnaire. The count data are described as frequencies and percentages, and the measurement data are represented as means and standard deviations. The general data of nurses during different time periods, the incidence of WPV, nurses' cognition and attitudes toward WPV and the attitudes and measures of hospitals regarding WPV were analyzed by the chi-square test. RESULTS: The incidence of WPV among nurses in Suzhou general hospitals in 2015 (69.0 %) and in 2019 (68.4 %) was higher than the incidence of 62.4 % in 2010 (P<0.05), and there were significant differences among periods in the specific types of violence (P˂0.05). Nurses who participated in the surveys in 2015 and 2019 scored higher on "having heard of WPV before", "thinking WPV coping management organizations are needed" and "supporting a zero-tolerance policy" than those who participated in 2010 (P<0.05). The attitudes and responses of hospitals with regard to WPV among nurses have greatly improved, as evidenced by the results for the items "offering training", "encouraging reporting of WPV to supervisors", "equipped with a WPV managing department", "handling WPV efficiently" and "hospital's attitudes" (P<0.005). CONCLUSIONS: Despite an increase in nurses' awareness and attitudes regarding WPV and significant improvements in hospitals' attitudes and responses to WPV, the incidence of WPV remains high. Hospitals should continue to explore scientific training modes that are in accordance with the needs of nurses to reduce the incidence of WPV.

Atomic Force Microscopy Based Top-Illumination Electrochemical Tip-Enhanced Raman Spectroscopy.

Electrochemical tip-enhanced Raman spectroscopy (EC-TERS) is a powerful technique for the in situ study of the physiochemical properties of the electrochemical solid/liquid interface at the nanoscale and molecular level. To further broaden the potential window of EC-TERS while extending its application to opaque samples, here, we develop a top-illumination atomic force microscopy (AFM) based EC-TERStechnique by using a water-immersion objective of a high numerical aperture to introduce the excitation laser and collect the signal. This technique not only extends the application of EC-TERS but also has a high detection sensitivity and experimental efficiency. We coat a SiO2 protection layer over the AFM-TERS tip to improve both the mechanical and chemical stability of the tip in a liquid TERS experiment. We investigate the influence of liquid on the tip-sample distance to obtain the highest TERS enhancement. We further evaluate the reliability of the as-developed EC-AFM-TERS technique by studying the electrochemical redox reaction of polyaniline. The top-illumination EC-AFM-TERS is promising for broadening the application of EC-TERS to more practical systems, including energy storage and (photo)electrocatalysis.

A genetic variant in the promoter of CD46 is associated with the risk and prognosis of hepatocellular carcinoma.

CD46 (also known as membrane cofactor protein), which is a member of the membrane-bound complement regulatory protein family, has been reported to cause cancer cells to escape complement-dependent cytotoxicity. However, the association between CD46 polymorphisms and the risk of hepatocellular carcinoma (HCC) has not been investigated. This two-stage association study was conducted to assess the relationship between the tagging single nucleotide polymorphisms (tagSNPs) of CD46 and HCC risk and prognosis. A series of functional analyses were performed to study the underlying mechanisms. Among the eight tagSNPs, rs2796267 (P = .003) and rs2796268 (P = .011) were found to modify HCC risk in the discovery set. Only rs2796267 (P < .0001) was confirmed to be associated with HCC susceptibility in the validation set. Compared with the wild-type AA genotype, the GG genotype significantly increased the HCC risk (adjusted odds ratio [OR] = 2.03; 95% confidence interval [CI], 1.34-3.08; P = .001). Moreover, subgroups analysis suggested a positive correlation among male and younger patients, especially among drinkers, smokers, and hepatitis B surface antigen-positive individuals. In functional analyses, we found that the rs2796267 G allele in the promoter region of CD46 could increase the expression of CD46 by affecting the binding affinity of STAT5a. Furthermore, Cox regression analysis revealed that the rs2796267 AG/GG genotype was significantly associated with worse prognosis of resected patients with HCC (hazard ratio = 2.27; 95% CI, 1.27-4.05; P = .006). These results suggest that the CD46 rs2796267 polymorphism may contribute to susceptibility and prognosis of HCC by altering promoter activity.

The MAPK kinase BcMkk1 suppresses oxalic acid biosynthesis via impeding phosphorylation of BcRim15 by BcSch9 in Botrytis cinerea.

The mitogen-activated protein kinase (MAPK) cassette of the cell wall integrity (CWI) pathway is primarily responsible for orchestrating changes of cell wall. However, functions of this cassette in other cellular processes are not well understood. Here, we found that the Botrytis cinerea mutant of MAPK kinase (BcMkk1) displays more serious defects in mycelial growth, conidiation, responses to cell wall and oxidative stresses, but possesses less reduced virulence than the mutants of its upstream (BcBck1) and downstream (BcBmp3) kinases. Interestingly, BcMkk1, but not BcBck1 and BcBmp3, negatively regulates production of oxalic acid (OA) and activity of extracellular hydrolases (EHs) that are proposed to be virulence factors of B. cinerea. Moreover, we obtained evidence that BcMkk1 negatively controls OA production via impeding phosphorylation of the Per-Arnt-Sim (PAS) kinase BcRim15 by the Ser/Thr kinase BcSch9. In addition, the fungal Pro40 homolog BcPro40 was found to interact simultaneously with three MAPKs, implying that BcPro40 is a scaffold protein of the CWI pathway in B. cinerea. Taken together, results of this study reveal that BcMkk1 negatively modulates virulence via suppressing OA biosynthesis in B. cinerea, which provides novel insight into conserved and species-specific functions of the MAPK kinase in fungi.

Protective role of overexpressed MUC5AC against fibrosis in MHV-68-induced combined pulmonary fibrosis and emphysema mouse model.

Mucins have long been regarded to play a role as a barrier to prevent mucosal infections; however, some studies report that overexpression of mucins induces obstruction and inflammation of airways. We investigated whether the secretion of overexpressed mucin, mucin5ac (MUC5AC), could improve protection against pathogens. To examine the possible roles of mucin hypersecretion in augmenting host defense against disease-promoting muco-obstructive lung disease, a mouse model that overexpressed MUC5AC was generated. We had previously proved that murine gammaherpesvirus-68 (MHV-68) infection could induce emphysema in mice, which later developed into combined pulmonary fibrosis and emphysema (CPFE). We further explored whether increased MUC5AC secretion could provide benefits against MHV-68 induced fibrosis. We initially developed a pcDNA3.1-MUC5AC mouse model. Next, the experimental mice were randomly divided into five groups: normal control, pcDNA3.1 control, pcDNA3.1-MUC5AC, CPFE, and pcDNA3.1- MUC5AC + CPFE. Morphometric analysis of each group was performed by hematoxylin and eosin staining and Masson trichrome staining. MUC5AC levels in lung tissues were analyzed by immunohistochemical staining, real-time polymerase chain reaction, and Western blot analysis. The airway inflammation was determined by differential cell counts of bronchoalveolar lavage fluid (BALF) and measurement of cytokines and chemokines in BALF by enzyme-linked immunosorbent assay. MUC5AC hypersecretion alone was not sufficient to drive goblet cell metaplasia to induce obvious mucus plugging and airway inflammation. However, MUC5AC overexpression served as a protective barrier against MHV-68 virus infection in vivo. Infectivity of MHV-68 was decreased in the pcDNA3.1-MUC5AC + CPFE group compared with that in CPFE group. Meanwhile, a reduction of MHV-68 virus attenuated the expressions of chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-X-C motif) ligand 5 (CXCL5), interleukin-13 (IL-13), and transforming growth factor-ß1 (TGF-ß1), and weakened airway inflammation and fibrosis in the pcDNA3.1-MUC5AC + CPFE group. Overexpression of MUC5AC appears to exhibit a protective role against MHV-68 infection in mice with emphysema that subsequently developed into CPFE and to further decrease airway inflammation and fibrosis induced by MHV-68 by decreasing the expressions of CCL2, CXCL5, IL-13, and TGF-ß1.