Causal association between immune cells and lung cancer risk: a two-sample bidirectional Mendelian randomization analysis.

Background: Previous studies have highlighted the crucial role of immune cells in lung cancer development; however, the direct link between immunophenotypes and lung cancer remains underexplored. Methods: We applied two-sample Mendelian randomization (MR) analysis, using genetic variants as instruments to determine the causal influence of exposures on outcomes. This method, unlike traditional randomized controlled trials (RCTs), leverages genetic variants inherited randomly at conception, thus reducing confounding and preventing reverse causation. Our analysis involved three genome-wide association studies to assess the causal impact of 731 immune cell signatures on lung cancer using genetic instrumental variables (IVs). We initially used the standard inverse variance weighted (IVW) method and further validated our findings with three supplementary MR techniques (MR-Egger, weighted median, and MR-PRESSO) to ensure robustness. We also conducted MR-Egger intercept and Cochran's Q tests to assess heterogeneity and pleiotropy. Additionally, reverse MR analysis was performed to explore potential causality between lung cancer subtypes and identified immunophenotypes, using R software for all statistical calculations. Results: Our MR analysis identified 106 immune signatures significantly associated with lung cancer. Notably, we found five suggestive associations across all sensitivity tests (P<0.05): CD25 on IgD- CD24- cells in small cell lung carcinoma (ORIVW =0.885; 95% CI: 0.798-0.983; P IVW =0.022); CD27 on IgD+ CD24+ cells in lung squamous cell carcinoma (ORIVW =1.054; 95% CI: 1.010-1.100; P IVW =0.015); CCR2 on monocyte cells in lung squamous cell carcinoma (ORIVW =0.941; 95% CI: 0.898-0.987; P IVW =0.012); CD123 on CD62L+ plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924-0.992; P IVW =0.017) as well as on plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924-0.992; P IVW =0.017) in lung squamous cell carcinoma. Conclusion: This study establishes a significant genomic link between immune cells and lung cancer, providing a robust basis for future clinical research aimed at lung cancer management.

Aldehyde dehydrogenase 2-mediated aldehyde metabolism promotes tumor immune evasion by regulating the NOD/VISTA axis.

BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme involved in endogenous aldehyde detoxification and has been implicated in tumor progression. However, its role in tumor immune evasion remains unclear. METHODS: Here, we analyzed the relationship between ALDH2 expression and antitumor immune features in multiple cancers. ALDH2 knockout tumor cells were then established using CRISPR/Cas9 system. In immunocompetent breast cancer EMT6 and melanoma B16-F10 mouse models, we investigated the impact of ALDH2 blockade on cytotoxic T lymphocyte function and tumor immune microenvironment by flow cytometry, mass cytometry, Luminex liquid suspension chip detection, and immunohistochemistry. Furthermore, RNA sequencing, flow cytometry, western blot, chromatin immunoprecipitation assay, and luciferase reporter assays were employed to explore the detailed mechanism of ALDH2 involved in tumor immune evasion. Lastly, the synergistic therapeutic efficacy of blocking ALDH2 by genetic depletion or its inhibitor disulfiram in combination with immune checkpoint blockade (ICB) was investigated in mouse models. RESULTS: In our study, we uncovered a positive correlation between the expression level of ALDH2 and T-cell dysfunction in multiple cancers. Furthermore, blocking ALDH2 significantly suppressed tumor growth by enhancing cytotoxic activity of CD8+ T cells and reshaping the immune landscape and cytokine milieu of tumors in vivo. Mechanistically, inhibiting ALDH2-mediated metabolism of aldehyde downregulated the expression of V-domain Ig suppressor of T-cell activation (VISTA) via inactivating the nucleotide oligomerization domain (NOD)/nuclear factor kappa-B (NF-κB) signaling pathway. As a result, the cytotoxic function of CD8+ T cells was revitalized. Importantly, ALDH2 blockade markedly reinforced the efficacy of ICB treatment. CONCLUSIONS: Our data delineate that ALDH2-mediated aldehyde metabolism drives tumor immune evasion by activating the NOD/NF-κB/VISTA axis. Targeting ALDH2 provides an effective combinatorial therapeutic strategy for immunotherapy.

Oncolytic virus oHSV2 combined with PD-1/PD-L1 inhibitors exert antitumor activity by mediating CD4 + T and CD8 + T cell infiltration in the lymphoma tumor microenvironment.

A novel therapeutic regimen showed that the oncolytic type II herpes simplex virus (oHSV2) was able to prevent colorectal cancer growth, recurrence, and metastasis. However, no study has yet explored whether oHSV2 has an impact on the development of diffuse large B-cell lymphoma (DLBCL). We chose the clinical chemotherapeutic drug doxorubicin (DOX) as a positive control to evaluate the effect of oHSV2 infection on the apoptotic, invasive, and proliferative capacity of DLBCL cells. We next further explored the therapeutic efficacy of oncolytic virus oHSV2 or DOX in DLBCL tumor bearing BALB/c mice, and evaluated the infiltration of CD8 + T cells and CD4 + T cells in tumor tissues. A pathological approach was used to explore the effects of oHSV2 on various organs of tumor bearing mice, including the heart, liver, and kidney. Next, SU-DHL-4 cells were co-cultured with cytotoxic T lymphocytes (CTLs) to mimic the tumor immune microenvironment (TME), to explore the impact of oHSV2 on the immune environment at the cellular level, and then analyzed the relationship between oHSV2 and the PD-1/PD-L1 immune-checkpoint. Subsequently, we further validated the efficacy of combined oHSV2 and PD-L1 treatment on transplanted tumor growth in mice at the in vivo level. DLBCL cells were sensitive to the action of the oncolytic virus oHSV2, and the decline in their proliferative activity showed a time-and dose-dependent manner. oHSV2 and DOX intervention preeminently increased the cell apoptosis, restrained cell proliferation and invasion, with the greatest changes occurring in response to oHSV2 infection. oHSV2 application effectively improved the immune status of the tumor microenvironment, favoring the invasion of CD8 + T and CD4 + T cells, thereby enhancing their antitumor effects. Besides, oHSV2 treatment has a safety profile in the organs of tumor bearing mice and indeed inhibits the PD-1/PD-L1 immune checkpoint in DLBCL. Interestingly, the combination of oHSV2 and PD-L1 antibodies results in more profound killing of DLBCL cells than oHSV2 infection alone, with a significant increase in the proportion of CD4 + T cells and CD8 + T cells. The antitumor effect was the best after combining oHSV2 and PD-L1 antibodies, suggesting that the combination therapy of oHSV2 and PD-L1 would have a better prospect for clinical application.

A Ribosome-Related Prognostic Signature of Breast Cancer Subtypes Based on Changes in Breast Cancer Patients' Immunological Activity.

Background and Objectives. The prognostic role of adjacent nontumor tissue in patients with breast cancer (BC) is still unclear. The activity changes in immunologic and hallmark gene sets in normal tissues adjacent to BC may play a crucial role in predicting the prognosis of BC patients. The aim of this study was to identify BC subtypes and ribosome-associated prognostic genes based on activity changes of immunologic and hallmark gene sets in tumor and adjacent nontumor tissues to improve patient prognosis. Materials and Methods. Gene set variation analysis (GSVA) was applied to assess immunoreactivity changes in the overall sample and three immune-related BC subtypes were identified by non-negative matrix factorization (NMF). KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) analyses were after determining the prognostic gene set using the least absolute shrinkage and selection operator (LASSO) method. Ribosome-related genes were identified by PPI (protein-protein interaction) analysis, and finally a prognostic risk model was constructed based on the expression of five ribosomal genes (RPS18, RPL11, PRLP1, RPL27A, and RPL38). Results. A comprehensive analysis of immune and marker genomic activity changes in normal breast tissue and BC tissue identified three immune-related BC subtypes. BC subtype 1 has the best prognosis, and subtype 3 has the worst overall survival rate. We identified a prognostic gene set in nontumor tissue by the least absolute shrinkage and selection operator (LASSO) method. We found that the results of both KEGG and GO analyses were indistinguishable from those of ribosome-associated genes. Finally, we determined that genes associated with ribosomes exhibit potential as a reliable predictor of overall survival in breast cancer patients. Conclusions. Our research provides an important guidance for the treatment of BC. After a mastectomy, the changes in gene set activity of both BC tissues and the nontumor tissues adjacent to it should be thoroughly evaluated, with special attention to changes in ribosome-related genes in the nontumor tissues.

Nickel-Doped Microfluidic Chip for Rapid and Efficient Immunomagnetic Separation and Detection of Breast Cancer Cell-Derived Exosomes.

Breast cancer cell-derived exosomes have high potential as biomarkers for continuous biopsies and longitudinal monitoring in breast cancer. However, it is extremely difficult to separate exosomes with high recovery and high purity from complex media, such as urine, plasma, saliva and cell culture supernatants. Here, we designed a flexible and simple microfluidic chip for exosome separation. The capture zone of the chip is a three-dimensional structure of interlaced cylinders doped with nickel powder. Exosomes were separated from cell culture supernatant by the immunomagnetic separation method in continuous flow mode and were detected by fluorescence imaging with high sensitivity. The chip achieved a high exosome recovery rate (> 74%) and purity (> 67%) at an injection rate of 3.6 mL/h. Thus, this chip was demonstrated to be a cutting-edge platform for the separation and detection of exosomes. It could also be applied to separate and detect other types of exosomes, microbubbles and cells.

Zingerone suppresses cell proliferation via inducing cellular apoptosis and inhibition of the PI3K/AKT/mTOR signaling pathway in human prostate cancer PC-3 cells.

Prostate cancer (PCa) is both the foremost and second cause of cancer death in the male population. Patients with hormone-dependent PCa are initially sensitive to androgen-deprivation therapy, later the cancer progress to a hormone-independent state and fails to respond and progress to the metastatic stage, where the cells gain the ability to escape cell death and develop resistance to current therapies, thereby leading to migration, invasion, and metastasis of cancer. Many clinical trials using nutraceuticals on cancer using human subjects have also been extensively studied, these studies confirm the efficacy of drugs tested in in vitro and in vivo preclinical models. Among various dietary phytochemicals, ginger is commonly used in the diet and possesses many active principles that act against cancer. Among various active principles, zingerone is a key active phenolic compound present in Zingiber officinale (Ginger), it has potent antioxidant property and it acts against carcinogens. The present study evaluated the efficacy of zingerone at different doses on the PCa cell line regarding apoptosis, upstream signing molecules such as Akt/mTOR, and migration metastasis. A cell viability assay using MTT was performed to estimate the percentage of viability of zingerone-treated PC-3 cells. The mitochondrial membrane potential, intracellular reactive oxygen species, and apoptosis induction in the zingerone-treated PC-3 cells were studied by using different fluorescence staining techniques. The expression patterns of PI3K, AKT, p-AKT, mTOR, and p-mTOR were investigated through the Western blot analysis assay. Zingerone induces apoptosis and alters Akt/mTOR molecules; it also inhibits cell adhesion and migration of PCa cells. From the present study, it is concluded that zingerone effectively induces apoptosis and inhibits cancer signaling, thereby acting as a potent drug against PCa.

Genome Recombination-Mediated tRNA Up-Regulation Conducts General Antibiotic Resistance of Bacteria at Early Stage.

Bacterial antibiotic resistance sets a great challenge to human health. It seems that the bacteria can spontaneously evolve resistance against any antibiotic within a short time without the horizontal transfer of heterologous genes and before accumulating drug-resistant mutations. We have shown that the tRNA-mediated translational regulation counteracts the reactive oxygen species (ROS) in bacteria. In this study, we demonstrated that isolated and subcultured Escherichia coli elevated its tRNAs under antibiotic stress to rapidly provide antibiotic resistance, especially at the early stage, before upregulating the efflux pump and evolving resistance mutations. The DNA recombination system repaired the antibiotic-induced DNA breakage in the genome, causing numerous structural variations. These structural variations are overrepresented near the tRNA genes, which indicated the cause of tRNA up-regulation. Knocking out the recombination system abolished the up-regulation of tRNAs, and coincidently, they could hardly evolve antibiotic resistance in multiple antibiotics, respectively. With these results, we proposed a multi-stage model of bacterial antibiotic resistance in an isolated scenario: the early stage (recombination-tRNA up-regulation-translational regulation); the medium stage (up-regulation of efflux pump); the late stage (resistant mutations). These results also indicated that the bacterial DNA recombination system and tRNA could be targeted to retard the bacterial spontaneous drug resistance.

Extent and risk factors of psychological violence towards physicians and Standardised Residency Training physicians: a Northern China experience.

PURPOSE: Physicians and Standardised Residency Training physicians (SRTPs) have relatively high exposure to psychological violence. Its adverse effects are far greater than those of physical violence. However, no previous research has paid attention to the problem of psychological violence among them. This study aims to evaluate the extent, characteristics, and risk factors of psychological violence among SRTPs in comparison to physicians, and also to highlight the psychological violence experienced by SRTPs and suggest preventive measures. METHODS: A cross-sectional survey was conducted in northern China. 884 physicians and 537 SRTPs completed a questionnaire which compiled by the ILO, ICN, WHO and PSI in 2003 to measure violence in the workplace. Descriptive statistics and logistic regression analysis were used to analyse results. RESULTS: The effective response rates of physicians and SRTPs were 63.1%(884/1400) and 86.3%(537/622) respectively. 73.0%(645/884) of physicians and 24.8%(133/537) of SRTPs suffered psychological violence in the past year. Compared to physicians (29/645, 4.5%), SRTPs (42/133, 31.6%) experience more internal violence. Further, after experiencing psychological violence, physicians are willing to talk to family and friends, but SRTPs generally take no action. Shift work was a risk factor for both physicians (OR 1.440, 95% CI 1.014-2.203) and SRTPs (OR 1.851, 95% CI 1.217-2.815) suffering from psychological violence. In contrast, no anxiety symptoms protected physicians (OR 0.406, 95% CI 0.209-0.789) and SRTPs (OR 0.404, 95% CI 0.170-0.959) against psychological violence. CONCLUSIONS: SRTPs and physicians in northern China have a high risk of experiencing psychological violence, and physicians experience more. Meanwhile, there are obvious differences in responses to psychological violence and risk factors between them. Therefore, medical institutions should pay more attention to psychological violence, especially among SRTPs, such as supporting the reporting of psychological violence, strengthening team relationships, and providing psychological comfort and counselling. Trial registration number (Project Identification Code: HMUIRB20160014), Registered May 10, 2016.

Workplace violence against healthcare professionals in a multiethnic area: a cross-sectional study in southwest China.

OBJECTIVE: The purpose of this study is to examine workplace violence (WPV) towards healthcare professionals in a multiethnic area in China, including prevalence, influencing factors, healthcare professionals' response to WPV, expected antiviolence training measures and content, and evaluation of WPV interventions. DESIGN: A cross-sectional study. SETTING: A grade III, class A hospital in the capital of Yunnan Province, which is the province with the most diverse ethnic minority groups in China. PARTICIPANTS: In total, 2036 healthcare professionals participated, with a response rate of 83.79%. RESULTS: The prevalence of physical and psychological violence was 5.5% and 43.7%, respectively. Healthcare professionals of ethnic minority were more likely to experience psychological violence (OR=1.54, 95% CI 1.16 to 2.05). Stratified by gender, male healthcare professionals of ethnic minority suffered from more physical violence (OR=3.31, 95% CI 1.12 to 9.79), while female healthcare professionals suffered from psychological violence (OR=1.71, 95% CI 1.24 to 2.36). We also found a unique work situation in China: overtime duty on-call work (18:00-07:00) was a risk factor for psychological violence (OR=1.40, 95% CI 1.02 to 1.93). Healthcare professionals of ethnic minority are less likely to order perpetrators to stop or to report to superiors when faced with psychological violence. They are also more interested in receiving training in force skills and self-defence. Both Han and ethnic minority participants considered security measures as the most useful intervention, while changing the time of shift the most useless one. CONCLUSION: Our study comprehensively described WPV towards healthcare professionals in a multiethnic minority area. More research on WPV conducted in multiethnic areas is needed.

miR-937 regulates the proliferation and apoptosis via targeting APAF1 in breast cancer.

Background: Previous research had shown that an imbalance in cell proliferation and apoptosis is a vital mechanism for tumorigenesis and cancer progression that may directly influence biological behaviors of cancer. microRNAs are associated with the occurrence and development of tumors. This study aimed to explore the influence of miR-937 on breast cancer regulation of APAF1 expression. Methods: Cancer Genome Altas microarray analysis (fold change > 2, p<0.05) was used to verify differentially expressed microRNAs and RT-qPCR was used to detect miR-937 mRNA level in breast cancer. Cell viability and proliferation were measured using CCK8 and colony formation assays, respectively, after the miR-937 mimics/inhibitors and their negative control were transfected into MCF7 cells. The variations in cell cycle and apoptosis were examined using flow cytometry. DAVID database was used to perform GO enrichment analysis. We use dual luciferase report system to detect the effect of miR-937 on the transcriptional activity of APAF1. APAF1 protein level was determined by Western blot assay. Results: miR-937 was up-regulated in breast cancer cell lines and high miR-937 expression is associated with a poorer survival rate in cancer patients. miR-937 overexpression promoted the viability, down-regulated the G1 phase ratios and increased the ability of colony formation in breast cancer cells. miR-937 inhibition inhibited the viability and the ability of colony formation, promoted the apoptosis and up-regulated the G1 phase ratios. Our results showed that miR-937 targeted bind to the APAF1-3'UTR. APAF1 overexpression inhibited the viability and the ability of colony formation, promoted the apoptosis and up-regulated the G1 phase ratios. After cells were co-transfection miR-937 mimics and APAF1, cell apoptosis level was increased. Conclusion: APAF1 up-regulation or APAF1 down-regulation in breast cancer may regulate cell proliferation and apoptosis.

PEG-coated and Gd-loaded fluorescent silica nanoparticles for targeted prostate cancer magnetic resonance imaging and fluorescence imaging.

Background: Multimodal imaging probes have become a powerful tool for improving detection sensitivity and accuracy, which are important in disease diagnosis and treatment. Methods: In this study, novel bifunctional magnetic resonance imaging (MRI)/fluorescence probes were prepared by loading gadodiamide into fluorescent silica nanoparticles (NPs) (Gd@Cy5.5@SiO2-PEG-Ab NPs) for targeting of prostate cancer (PCa). The physicochemical characteristics, biosafety and PCa cell targeting ability of the Gd@Cy5.5@SiO2-PEG-Ab NPs were studied in vitro and in vivo. Results: The Gd@Cy5.5@SiO2-PEG-Ab NPs had a spherical morphology with a relatively uniform size distribution and demonstrated high efficiency for Gd loading. In vitro and in vivo cell-targeting experiments demonstrated a high potential for the synthesized NPs to target prostate-specific membrane antigen (PSMA) receptor-positive PCa cells, enabling MRI and fluorescence imaging. In vitro cytotoxicity assays and in vivo hematological and pathological assays showed that the prepared NPs exhibited good biological safety. Conclusion: Our study demonstrates that the synthesized Gd@Cy5.5@SiO2-PEG-Ab NPs have great potential as MRI/fluorescence contrast agents for specific identification of PSMA receptor-positive PCa cells.

A cross-sectional survey on patient safety culture in secondary hospitals of Northeast China.

OBJECTIVES: This study aims to investigate patient safety culture in secondary hospitals of Heilongjiang, Northeast China, and explore the implications of patient safety culture and practices through the perspectives of various healthcare workers. METHODS: A cross-sectional survey using the Safety Attitude Questionnaire (SAQ) was conducted to ascertain the status of patient safety culture in nine secondary hospitals across the six dimensions of the SAQ. Among the 900 staff members who were invited to participate, 665 completed the questionnaire. Descriptive statistics were used to calculate the general means and standard deviations of the patient safety culture dimensions and other numerical variables, and F-test and a multivariate regression analysis were used to statistically analyze the differences in perceptions of safety culture considering the differences in demographic characteristics. All statistical analyses were performed using SPSS v. 22.0. RESULTS: The respondents rated job satisfaction as the highest among all six dimensions of the SAQ, followed in order by teamwork climate, working conditions, and stress recognition (the lowest). There were significant differences among the dimensions of patient safety culture and other factors, such as gender, age, job position, and education. Compared with previous studies, teamwork climate and working conditions scores were quite high, while stress recognition score was very low. We also found differences in patient safety culture by demographic characteristics. CONCLUSIONS: The findings revealed the patient safety culture attitudes of healthcare workers in secondary hospitals of Heilongjiang, and provided baseline data for related future research. This evidence may also help government health policymakers and hospital administrators understand related challenges and develop strategies to improve patient safety culture in secondary hospitals of China and perhaps also in other developing countries.

Perceptions of patient safety culture among medical students: a cross-sectional investigation in Heilongjiang Province, China.

OBJECTIVES: Medical school education plays an important role in promoting patient safety. In this study, we assess medical students' perceptions of patient safety culture, identify their educational needs and provide evidence on the most important content relating to patient safety for the medical school curriculum. METHOD: This cross-sectional study was conducted in four medical universities in Heilongjiang province. Medical students in the first through five years completed an anonymous questionnaire-the Attitudes toward Patient Safety Questionnaire III. We analysed the differences in responses across the four universities and their cohorts. RESULTS: The overall perceptions of patient safety culture across the four medical universities were positive. The highest positive response rate was for 'I have a good understanding of patient safety issues as a result of my undergraduate medical training' (range: 58.4%-99.8%), whereas the lowest positive response rate was for 'medical errors are a sign of incompetence' (14.7%-47.9%). Respondents in the earlier years of school tended to have more positive responses for items concerning working hours and team work; however, fourth and fifth year students had more positive responses for error inevitability. Items with the lowest positive response rates across the cohorts included items related to 'professional incompetence as a cause of error' and 'disclosure responsibility'. CONCLUSIONS: While students generally had positive views of patient safety culture, none of them had been exposed to any formal curriculum content on patient safety. Policymakers should focus more on how educational needs vary across schools and cohorts in order to establish appropriate curricula.

Psychological violence against general practitioners and nurses in Chinese township hospitals: incidence and implications.

BACKGROUND: International reports indicating that around 10-50% of health care staff are exposed to violence every year; in certain settings, this rate might reach over 85%. Evidence has shown that people who experience psychological violence are seven times as likely to be victims of physical violence. Although there have been numerous studies on WPV in general hospitals, there is no consensus regarding the current status of psychological violence directed at health care workers in township hospitals in China. The purpose of this study was to estimate the prevalence and the risk factors of psychological violence in Chinese township hospitals. METHODS: A retrospective cross-sectional survey of township hospitals general practitioners and general nurses was conducted in Heilongjiang Province, China.Descriptive analyses and binary logistic regression analysis were used to estimated the prevalence and the risk factors of psychological violence. RESULTS: Regardless of whether the assessment period was the past 12 months, past 36 months, or during their entire career,GPs and nurses reported that verbal abuse was the most common type of psychological violence (28.05, 30.28, 38.69 and 40.45%, 43.86, 54.02%).The main perpetrator was patients' relatives. Most participants responded to violence with "pretend nothing happened", 55.63% of GPs and 62.64% of nurses reported that the perpetrator received no punishment. Around 47.62% of respondents reported that their workplace had no procedures for reporting violence. When workplaces did have a reporting system, 57.73% knew how to use them. Only 36.98% had training in managing aggression and violence. General nurses, individuals 35 years or younger, those with higher professional titles and who work in shifts are at greater risk of psychological violence. CONCLUSIONS: Our results indicate a high prevalence of psychological violence in Chinese township hospitals, which can no longer be ignored. Effective measures should be taken to prevent and respond to workplace violence(WPV), especially psychological violence. TRIAL REGISTRATION: (Project Identification Code: HMUIRB20160014), Registered May 10, 2016.

Novel gadopentetic acid-doped silica nanoparticles conjugated with YPSMA-1 targeting prostate cancer for MR imaging: an in vitro study.

The early diagnosis of prostate cancer (PCa) is particularly important for reducing its high mortality rate. With the development of molecular magnetic resonance imaging (MRI), early diagnosis via non-invasive imaging has become possible. In this study, gadopentetic acid (GA)-doped silica (Gd@SiO2) was first synthesized by a reverse microemulsion method, and amino and carboxyl groups were then successively introduced onto the surface of this Gd@SiO2. After these steps, a monoclonal antibody (YPSMA-1) to prostate-specific membrane antigen (PSMA) was conjugated with carboxyl-modified Gd@SiO2 (Gd@SiO2-COOH) nanoparticles (NPs) by the carbodiimide method. Gd@SiO2-Ab NPs were thus obtained as specific MR contrast agents for PCa-targeted imaging. Transmission electron microscopy showed that the Gd@SiO2-Ab NPs exhibited a dispersed spherical morphology with a relatively uniform size distribution. The Gd@SiO2-Ab NPs showed high stability and high the longitudinal relaxation rate (r1). Cell-targeting experiments in vitro demonstrated the high potential of the synthesized NPs to target PSMA receptor-positive PCa cells. In vitro cytotoxicity assays showed that the Gd@SiO2-Ab NPs exhibited good biological safety. These results suggest that the synthesized Gd@SiO2-Ab NPs have great potential as specific MR contrast agents for PSMA receptor-positive PCa cells.

Depressive symptoms and workplace-violence-related risk factors among otorhinolaryngology nurses and physicians in Northern China: a cross-sectional study.

OBJECTIVES: Workplace violence is relatively frequent among medical professionals who work in otorhinolaryngology units. This phenomenon reduces the quality of provided medical care and increases the incidence of depressive symptoms among physicians and nurses, seriously affecting their job satisfaction and work efficiency with a negative attitude towards providing treatment. Few existing studies have assessed workplace-violence-related factors associated with depressive symptoms among otorhinolaryngology physicians and nurses. METHODS: We conducted a cross-sectional study in grade A tertiary hospitals of Heilongjiang province in Northern China, to evaluate the occurrence and level of depressive symptoms among otorhinolaryngology physicians and nurses and to analyse the relationship between them and workplace-violence-related risk factors and demographic variables. RESULTS: Of all our participating professionals, (379 otorhinolaryngologists and 273 nurses), 57.2% were found to have depressive symptoms, whereas, of the respondents who had suffered from physical violence, 71.25% had depressive symptoms. Professionals with less than 1 year of experience, as well as professionals who more frequently worked alone, were more likely to suffer from depressive symptoms than their colleagues. CONCLUSIONS: This research addresses an emerging issue of clinical practice, and its results differ from those of previous studies; specifically, it indicates that the frequency of depressive symptoms among otorhinolaryngology physicians and nurses may be influenced by physical violence, the number of coworkers they have for more than half of their working hours and other workplace-violence-related factors. To reduce the depressive symptoms caused by workplace violence and improve the quality of medical services, medical institutions should implement effective measures to prevent the occurrence of physical violence, strengthen team cooperation ability and increase peer support.

Comparison of enhancement of anaerobic digestion of waste activated sludge through adding nano-zero valent iron and zero valent iron.

The feasibility of adding nano-zero valent iron (NZVI: 0.6, 1.0, 4.0, 10.0 g L-1) to enhance anaerobic digestion of waste activated sludge (WAS) was examined by comparison with ZVI, and the mechanisms of NZVI enhancement of the hydrolysis and methanogenesis processes were elucidated. NZVI could enhance hydrolysis-acidification of WAS by destroying the integrity of microbial cells. Both volatile fatty acids production and the acetic acid portion were greatly improved by NZVI additions, peaking at 4.0 g L-1 NZVI. In anaerobic digestion, CH4 production was promoted at a NZVI dosage ≤1.0 g L-1. The optimum dosage of NZVI for methanogenesis was 1.0 g L-1, and further addition of NZVI could cause inhibition of methanogenesis because of long-term accumulation of H2. ZVI could also improve hydrolysis-acidification and the CH4 yield, but its efficiency was relatively low compared with NZVI, and it could not induce cell wall rupture. 16S rDNA high-throughput sequencing results showed that NZVI addition at appropriate dosage facilitated increasing the proportion of microorganisms involved in WAS hydrolysis-acidification and methanogenesis.

Effects of xylitol dehydrogenase (XYL2) on xylose fermentation by engineered Candida glycerinogenes.

Efficient bioconversion of d-xylose into various biochemicals is critical for lignocelluloses application. Candida glycerinogenes, expressing the xylitol dehydrogenase (XYL2) gene, has the ability to produce glycerol from xylose entered into pentose phosphate pathway. In this study, we demonstrate that low expression levels of the XYL2 gene derived from Scheffersomyces stipitis in C. glycerinogenes is a major bottleneck in efficient xylose fermentation. Through a metabolic engineering approach using an integrative expression, XYL2 was identified as an overexpression target for improving xylose metabolism. Two recombinant strains with XYL2 overexpression were constructed to ferment a mixture of glucose and xylose simultaneously in batch fermentation. Compared with C. glycerinogenes (wild type), glycerol production from xylose by C. glycerinogenes (PURGAPX2) and C. glycerinogenes (PURGPDX2) was increased by 94.5% and 103.3%, respectively. It was also found that additional overexpression of XYL2 under the control of strong promoters in a xylose-fermenting strain not only reduced xylitol accumulation but also increased glycerol yields. As the expression levels of XYL2 increased, the glycerol yields gradually improved from 30.6 to 63.3 g/L, whereas the xylitol yields significantly decreased from 38.7 to 19.9 g/L. These results suggest that strong expression of XYL2 is a necessary condition for developing efficient xylose-fermenting strains.

Role of CgHOG1 in Stress Responses and Glycerol Overproduction of Candida glycerinogenes.

Candida glycerinogenes, the glycerol producer with excellent multi-stress tolerances, is considered to be a potential biotechnological host used in the production of glycerol and its derivatives under extreme fermentation conditions. In this study, to evaluate the multiple roles of mitogen-activated protein kinase CgHOG1, we constructed a gene disruption system in the diploid C. glycerinogenes to obtain CgHOG1 null mutant. Pseudohyphae generation of the CgHOG1 mutant under non-inducing condition indicated a repressor role in morphological transitions. Disruption of CgHOG1 resulted in increased sensitivities to osmotic, acetic acid, and oxidative stress but not involved in thermotolerance. In the CgHOG1 mutant, NaCl shock failed to stimulate the accumulation of intracellular glycerol and was fatal. In addition, the CgHOG1 mutant displayed a significant prolonged growth lag phase in YPD medium with no decrease in glycerol production, whereas the mutant cannot grow under hyperosmotic condition with no detectable glycerol in broth. These results suggested that CgHOG1 plays important roles in morphogenesis and multi-stress tolerance. The growth and glycerol overproduction under osmotic stress are heavily dependent on CgHOG1 kinase.