Sodium para-aminosalicylic acid attenuates combined manganese/iron-induced cortical synaptic damage in rats.

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment.

Clinical case analysis of 32 children aged 0-6 years with lead poisoning in Nanning, China.

Lead is one of the heavy metals that is toxic and widely distributed in the environment, and children are more sensitive to the toxic effects of lead because the blood-brain barrier and immune system are not yet well developed. The objective of the study was to investigate the clinical characteristics of lead poisoning in children aged 0∼6 years in a hospital in Guangxi, and to provide scientific basis for the prevention and treatment of lead poisoning. We collected and analyzed the clinical data of 32 children with lead poisoning admitted to a hospital in Guangxi from 2010 to 2018. The results showed that most of the 32 cases presented with hyperactivity, irritability, poor appetite, abdominal pain, diarrhea, or constipation. The hemoglobin (HGB), mean corpusular volume (MCV), mean corpuscular hemoglobin (MCH), and hematocrit (HCT) of the lead-poisoned children were all decreased to different degrees and were below normal acceptable levels. Urinary ß2-microglobulin was increased. Blood lead levels (BLL) decreased significantly after intravenous injection of the lead chelator, calcium disodium edetate (CaNa2-EDTA). In addition, HGB returned to normal levels, while MCV, MCH, and HCT increased but remained below normal levels. Urinary ß2-microglobulin was reduced to normal levels. Therefore, in this cohort of children, the high-risk factors for lead poisoning are mainly Chinese medicines, such as baby powder. In conclusion, lead poisoning caused neurological damage and behavioral changes in children and decreased erythrocyte parameters, leading to digestive symptoms and renal impairment, which can be attenuated by CaNa2-EDTA treatment.

Effects of Manganese and Iron, Alone or in Combination, on Apoptosis in BV2 Cells.

The aim of study was to address the effects of manganese and iron, alone and in combination, on apoptosis of BV2 microglia cells, and to determine if combined exposure to these metals augments their individual toxicity. We used a murine microglial BV2 cell line. Cell cytotoxicity was analyzed by propidium iodide (PI) exclusion assay. Cell ROS production was analyzed by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) probe staining. Pro-inflammatory cytokine production was monitored by ELISA. Cell apoptosis was analyzed by PE Annexin V/7-AAD staining. Mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting to analyze the effect of manganese, iron alone, or their combined exposure on the activation of caspase9, P53, Bax, and Bcl2 apoptosis signaling pathways. Caspase3 activity was determined using a Colorimetric. Manganese, iron, and their combined exposure for 24 h induced the activation of BV2 microglia cells and increased ROS production and the expression of the inflammatory cytokines, IL-1ß and TNF-α. And we also found that the apoptosis rate increased, mitochondrial membrane potential decreased, apoptosis-related proteins caspase9, P53, Bax, and Bcl2 expression increased, and caspase3 activity increased. Furthermore, we found that combined manganese-iron cytotoxicity was lower than that induced by manganese exposure alone. Manganese, iron alone, or their combination exposure can induce apoptosis in glial cells. Iron can reduce the toxicity of manganese, and there is an antagonistic effect between manganese and iron.

Combined exposure to manganese and iron decreases oxidative stress-induced nerve damage by increasing Nrf2/HO-1/NQO1 expression.

BACKGROUND: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. METHODS: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. RESULTS: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. CONCLUSION: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.

Signal Transduction Associated with Mn-induced Neurological Dysfunction.

Manganese (Mn) is a heavy metal that occurs widely in nature and has a vital physiological role in growth and development. However, excessive exposure to Mn can cause neurological damage, especially cognitive dysfunction, such as learning disability and memory loss. Numerous studies on the mechanisms of Mn-induced nervous system damage found that this metal targets a variety of metabolic pathways, for example, endoplasmic reticulum stress, apoptosis, neuroinflammation, cellular signaling pathway changes, and neurotransmitter metabolism interference. This article reviews the latest research progress on multiple signaling pathways related to Mn-induced neurological dysfunction.

Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation.

CXCR4 is a key regulator of the development of NK cells and DCs, both of which play an important role in early placental development and immune tolerance at the maternal-fetal interface. However, the role of CXCR4 in pregnancy is not well understood. Our study demonstrates that adult-induced global genetic CXCR4 deletion, but not uterine-specific CXCR4 deletion, was associated with increased pregnancy resorptions and decreased litter size. CXCR4-deficient mice had decreased NK cells and increased granulocytes in the decidua, along with increased leukocyte numbers in peripheral blood. We found that CXCR4-deficient mice had abnormal decidual NK cell aggregates and NK cell infiltration into trophoblast areas beyond the giant cell layer. This was associated with low NK cell expression of granzyme B, a NK cell granule effector, indicative of NK cell dysfunction. Pregnancy failure in these mice was associated with abnormalities in placental vascular development and increased placental expression of inflammatory genes. Importantly, adoptive BM transfer of WT CXCR4+ BM cells into CXCR4-deficient mice rescued the reproductive deficits by normalizing NK cell function and mediating normal placental vascular development. Collectively, our study found an important role for maternal CXCR4 expression in immune cell function, placental development, and pregnancy maintenance.

A novel nomogram for predicting post-recurrence survival in recurrent neuroblastoma patients.

Patients with recurrent neuroblastoma (NB) have a broad range of prognoses. This research aimed to develop a nomogram to assess post-recurrence survival (PRS) in patients with recurrent neuroblastoma. The TARGET database was utilized to enroll 825 individuals diagnosed with neuroblastoma between 1986 and 2012, 250 of whom were diagnosed with recurrent NB. These patients were randomly divided into a training group (n = 175) and a validation group (n = 75) at a ratio of 7:3. The Kaplan-Meier method was used for survival analysis. A prognosis nomogram was constructed based on post-recurrence survival indicators identified through Cox regression and LASSO analysis. The nomogram's capability for classification and calibration was assessed using the calibration curve, the area under the time-dependent receiver operating characteristic curve (AUC), and the consistency index (C-index). The nomogram was verified in the validation cohort, and its clinical applicabilities were assessed using the decision curve analysis (DCA). Four PRS predictors, COG risk group, INSS stage, MYCN status, and age, were identified to construct the nomogram, which showed good discrimination and calibration in the training and validation sets. The C-index of the training and validation sets was 0.681 [95% confidence interval (CI), 0.632-0.730] and 0.666 [95% CI, 0.593-0.739], respectively. The nomogram's AUC values for the training and validation sets at 1, 3, and 5 years were 0.747, 0.775, and 0.782 vs. 0.721, 0.757, and 0.776. The nomogram's AUC values were consistently higher than those of the COG risk groups and INSS stage, indicating that the nomogram had superior differentiation compared to the INSS stage and COG risk group. The DCA curve also demonstrated that the nomogram we developed outperformed conventional COG risk groups and INSS stage regarding clinical advantage. In the present study, we developed and validated a novel nomogram that should facilitate more accurate and personalized assessment of the survival probability of children with relapsed neuroblastoma. This model should assist physicians in their clinical decision-making process.

Effects of sodium para-aminosalicylic acid on chelation treatment in Pb-exposed mice.

Lead (Pb) is a corrosion-resistant, heavy, non-ferrous metal. Several metal chelators have been used for the treatment of Pb poisoning. However, the efficacy of sodium para-aminosalicylic acid (PAS-Na) in enhancing Pb excretion has yet to be fully characterized. Healthy male mice (90) were divided into six groups, the normal control group was intraperitoneally (i.p.) injected with saline and the remaining group of mice i.p. 120 mg/kg Pb acetate. Four hour later, mice were subcutaneously (back) injected (s.c.) with (80, 160, 240 mg/kg) PAS-Na or 240 mg/kg edetate calcium disodium (CaNa2EDTA) or an equivalent amount of saline, once per day for 6 days. After 24-h urine sample collections, the animals were anesthetized with 5% chloral hydrate and sacrificed in batches on the 2nd, 4th, or 6th day. Levels of Pb [including manganese (Mn) and copper (Cu)] in the urine, whole blood, and brain tissues were analyzed by graphite furnace atomic absorption spectrometry. The results showed that Pb exposure increased its levels in urine and blood, and PAS-Na treatment may afford antagonistic effect on Pb poisoning, suggesting that PAS-Na is a potentially effective treatment to promote excretion of Pb.

Protective Effects of Sodium Para-Aminosalicylic Acid on Lead and Cadmium Co-Exposure in SH-SY5Y Cells.

BACKGROUND: Combined exposure to lead and cadmium is common in occupational environments. However, the effects of co-exposure to Pb-Cd on neurotoxicity have not been fully clarified. Sodium para-aminosalicylic acid (PAS-Na) has previously been shown to protect neurons from Pb-induced toxicity. This study aimed to investigate the beneficial effect of PAS-Na against co-exposure to Pb-Cd-induced neurodegeneration in SH-SY5Y cells. METHODS: The MTT assay was used to detect the effects of Pb and Cd alone, or in combination, on SH-SY5Y cell survival. The effects of Pb and Cd alone or in combination on oxidative stress were assessed by reactive oxygen species (ROS) level. Nrf2, the master switch for antioxidant responses, was detected by immunofluorescence. Protein expression levels of PI3K, Akt, p-Akt, Nrf2 and HO-1 were determined by Western blot analysis. RESULTS: MTT assay results established that the survival rate of SH-SY5Y cells was not significantly affected by exposure to 1 µmol/L lead, 0.25 µmol/L cadmium, and 1-fold Pb-Cd mixture (1 µmol/L Pb + 0.25 µmol/L Cd), while 10-fold Pb-Cd combined exposure (10 µmol/L Pb + 2.5 µmol/L Cd) significantly reduced the survival rate of SH-SY5Y cells. Combined Pb-Cd exposure significantly increased intracellular ROS levels, and N-Acetyl-L-cysteine (NAC) treatment in the 10 µmol/L Pb + 2.5 µmol/L Cd group significantly decreased ROS expression levels, attenuating the levels of oxidative stress. Protein expression of PI3K and p-Akt significantly decreased in the 10 µmol/L Pb + 2.5 µmol/L Cd group, while the expression of PI3K and p-Akt protein increased after PAS-Na intervention. Immunofluorescence analysis showed that levels of Nrf2 in the nucleus increased in the 10 µmol/L Pb + 2.5 µmol/L Cd group, along with Nrf2 protein levels, suggesting that Nrf2 was translocated from the cytoplasm into the nucleus upon combined Pb-Cd exposure. In addition, HO-1 protein expression level, a downstream gene product of Nrf2, was increased. In response to NAC intervention, HO-1 protein expression levels significantly decreased. PAS-Na had the same intervention effect as NAC. CONCLUSION: Combined exposure to Pb-Cd induced oxidative stress and cytotoxicity in SH-SY5Y cells. PAS-Na displayed antagonistic effects on neurodegenerative changes induced by combined Pb-Cd exposure; hence, it may afford a novel treatment modality for exposure to these metals.

Risk and Protective Profile of Men Who Have Sex With Men Using Mobile Voluntary HIV Counseling and Testing: Latent Class Analysis.

BACKGROUND: Mobile voluntary counseling and testing (VCT) for HIV has been carried out to improve the targeting of at-risk populations and HIV case detection for men who have sex with men (MSM). However, the HIV-positive detection rate using this screening strategy has declined in recent years. This may imply unknown changes in risk-taking and protective features jointly influencing the testing results. These changing patterns in this key population remain unexplored. OBJECTIVE: The aim of this study was to identify the nuanced group classification of MSM who underwent mobile VCT using latent class analysis (LCA), and to compare the difference in characteristics and testing results between subgroups. METHODS: A cross-sectional research design and purposive sampling were applied between May 21, 2019, and December 31, 2019. Participants were recruited by a well-trained research assistant through social networking platforms, including the most popular instant messenger app Line, geosocial network apps dedicated to MSM, and online communities. Mobile VCT was provided to participants at an assigned time and place. Demographic characteristics and risk-taking and protective features of the MSM were collected via online questionnaires. LCA was used to identify discrete subgroups based on four risk-taking indicators-multiple sexual partners (MSP), unprotected anal intercourse (UAI), recreational drug use within the past 3 months, and history of sexually transmitted diseases-and three protective indicators-experience of postexposure prophylaxis, preexposure prophylaxis use, and regular HIV testing. RESULTS: Overall, 1018 participants (mean age 30.17, SD 7.29 years) were included. A three-class model provided the best fit. Classes 1, 2, and 3 corresponded to the highest risk (n=175, 17.19%), highest protection (n=121, 11.89%), and low risk and low protection (n=722, 70.92%), respectively. Compared to those of class 3, class 1 participants were more likely to have MSP and UAI within the past 3 months, to be ≥40 years of age (odds ratio [OR] 2.197, 95% CI 1.357-3.558; P=.001), to have HIV-positive results (OR 6.47, 95% CI 2.272-18.482; P<.001), and a CD4 count ≤349/µL (OR 17.50, 95% CI 1.223-250.357; P=.04). Class 2 participants were more likely to adopt biomedical preventions and have marital experience (OR 2.55, 95% CI 1.033-6.277; P=.04). CONCLUSIONS: LCA helped derive a classification of risk-taking and protection subgroups among MSM who underwent mobile VCT. These results may inform policies for simplifying the prescreening assessment and more precisely recognizing those who have higher probabilities of risk-taking features but remain undiagnosed targets, including MSM engaging in MSP and UAI within the past 3 months and those ≥40 years old. These results could be applied to tailor HIV prevention and testing programs.

Sodium Para-Aminosalicylic Acid Modulates Autophagy to Lessen Lead-Induced Neurodegeneration in Rat Cortex.

Lead (Pb) is a common heavy metal contaminant in the environment, and it may perturb autophagy and cause neurodegeneration. Although sodium para-aminosalicylic (PAS-Na) has been shown to protect the brain from lead-induced toxicity, the mechanisms associated with its efficacy have yet to be fully understood. In this study, we evaluated the efficacy of PAS-Na in attenuating the neurotoxic effects of lead, as well as the specific mechanisms that mediate such protection. Lead exposure resulted in weight loss and injury to the liver and kidney, and PAS-Na had a protective effect against this damage. Both short-term and subchronic lead exposure impaired learning ability, and this effect was reversed by PAS-Na intervention. Lead exposure also perturbed autophagic processes through the modulation of autophagy-related factors. Short-term lead exposure downregulated LC3 and beclin1 and upregulated the expression of p62; subchronic lead exposure upregulated the expression of LC3, beclin1, and P62. It follows that PAS-Na had an antagonistic effect on the activation of the above autophagy-related factors. Overall, our novel findings suggest that PAS-Na can protect the rat cortex from lead-induced toxicity by regulating autophagic processes. (1) Short-term lead exposure inhibits autophagy, whereas subchronic lead exposure promotes autophagy. (2) PAS-NA ameliorated the abnormal process of lead-induced autophagy, which had a protective effect on the cerebral cortex.

Return to work in head and neck cancer survivors: its relationship with functional, psychological, and disease-treatment factors.

PURPOSE: Return to work (RTW) is important for survivors of head and neck cancer (HNC). The purposes of the study were to investigate the RTW ratio among HNC survivors and identify factors significantly affecting RTW in this population. METHODS: A cross-sectional study with consecutive sampling was conducted in a medical center in Taiwan, with 111 patients with HNC who had completed major treatments within 5 years and were employed before their cancer diagnosis enrolled as participants. Cervical range of motion (CROM) functionality, handgrip and hip flexor strength, maximal mouth opening (MMO), selected symptoms, depression, and disease/treatment-related factors were assessed. All of the factors were analyzed using t-test, chi-square test, and multiple logistic regression. RESULTS: Less than half (44.1%, n = 49) of the participants had returned to work. The t-test/chi-square test results showed the RTW group to be younger in age and better educated; have better handgrip/hip flexor strength, MMO, and CROM; have less speech difficulty and pain; and have less-advanced cancer than the non-RTW group. Further analysis of the above significant variables by logistic regression revealed early cancer stage, dominant handgrip strength, and less speech difficulty were the robust factors related to RTW. CONCLUSIONS: The RTW ratio is low in HNC survivors. RTW in HNC survivors is a multifactorial and complicated issue and needs to be further examined. IMPLICATIONS FOR CANCER SURVIVORS: Assessing the factors related to RTW systematically and developing comprehensive interventions and rehabilitation programs to reduce related dysfunctions are necessary to enhance RTW ability in HNC survivors.

Effect of Occupational Extremely Low-Frequency Electromagnetic Field Exposure on the Thyroid Gland of Workers: A Prospective Study.

OBJECTIVE: The aim of this study was to investigate the biological effects of occupational extremely low-frequency electromagnetic field (ELF-EMF) exposure on the thyroid gland. METHODS: We conducted a prospective analysis of 85 workers (exposure group) exposed to an ELF-EMF (100 µT, 10-100 Hz) produced by the electromagnetic aircraft launch system and followed up on thyroid function indices, immunological indices, and color Doppler images for 3 years. Additionally, 116 healthy volunteers were randomly selected as controls (control group), the thyroid function of whom was compared to the exposure group. RESULTS: No significant difference was observed in thyroid function between the exposure and control groups. During the follow-up of the exposure group, the serum free triiodothyronine (FT3) level was found to slowly decrease and free thyroxine (FT4) level slowly increase with increasing exposure time. However, no significant difference was found in thyroid-stimulating hormone (TSH) over the three years, and no significant difference was observed in the FT3, FT4 and TSH levels between different exposure subgroups. Furthermore, no significant changes were observed in thyroid autoantibody levels and ultrasound images between subgroups or over time. CONCLUSION: Long-term exposure to ELF-EMF may promote thyroid secretion of T4 and inhibit deiodination of T4 to T3. ELF-EMF has no significant effect on thyroid immune function and morphology.

[The Physical and Psychological Impacts and Supportive Care Needs of Patients With Cancer Undergoing Immunotherapy and Their Family Caregivers].

New, science-based cancer treatments have proliferated in recent years. Immunotherapy provides new hope for prolonging survival in patients with advanced-stage cancers. However, patients with cancer must not only face their disease progression, physical, and psychological symptoms, but also deal with the side effects and efficacy of immunotherapy. Patients with cancer may experience complex emotions such as fear, anxiety, depression, or uncertainty relatively frequently and may have many unmet care needs specific to immunotherapy. However, articles on the physical and psychological impacts and supportive care needs experienced by patients with advanced-stage cancers undergoing immunotherapy and their family caregivers are limited in the literature. Thus, this paper was developed to present (1) a brief introduction to cancer immunotherapy; (2) the physical and psychological impacts experienced by patients with cancer undergoing immunotherapy and their caregivers; (3) the status of the supportive care needs of patients and family caregivers during the immunotherapy process; and (4) an assessment of and intervention to address the supportive care needs of these patients with cancer and their caregivers. We hope this article will help clinical healthcare providers understand the physical and psychological impacts and supportive care needs of advanced patients with cancer and their family caregivers during the immunotherapy process. Furthermore, we suggest that appropriate medical care be provided or developed in the future to improve their quality of life during the immunotherapy process and to enhance clinical practices.

Risk factors for hospital readmissions in pneumonia patients: A systematic review and meta-analysis.

BACKGROUND: Factors that are associated with the short-term rehospitalization have been investigated previously in numerous studies. However, the majority of these studies have not produced any conclusive results because of their smaller sample sizes, differences in the definition of pneumonia, joint pooling of the in-hospital and post-discharge deaths and lower generalizability. AIM: To estimate the effect of various risk factors on the rate of hospital readmissions in patients with pneumonia. METHODS: Systematic search was conducted in PubMed Central, EMBASE, MEDLINE, Cochrane library, ScienceDirect and Google Scholar databases and search engines from inception until July 2021. We used the Newcastle Ottawa (NO) scale to assess the quality of published studies. A meta-analysis was carried out with random-effects model and reported pooled odds ratio (OR) with 95% confidence interval (CI). RESULTS: In total, 17 studies with over 3 million participants were included. Majority of the studies had good to satisfactory quality as per NO scale. Male gender (pooled OR = 1.22; 95%CI: 1.16-1.27), cancer (pooled OR = 1.94; 95%CI: 1.61-2.34), heart failure (pooled OR = 1.28; 95%CI: 1.20-1.37), chronic respiratory disease (pooled OR = 1.37; 95%CI: 1.19-1.58), chronic kidney disease (pooled OR = 1.38; 95%CI: 1.23-1.54) and diabetes mellitus (pooled OR = 1.18; 95%CI: 1.08-1.28) had statistically significant association with the hospital readmission rate among pneumonia patients. Sensitivity analysis showed that there was no significant variation in the magnitude or direction of outcome, indicating lack of influence of a single study on the overall pooled estimate. CONCLUSION: Male gender and specific chronic comorbid conditions were found to be significant risk factors for hospital readmission among pneumonia patients. These results may allow clinicians and policymakers to develop better intervention strategies for the patients.

Related factors influencing Chinese psychiatric nurses' turnover: A cross-sectional study.

WHAT IS KNOWN ON THE SUBJECT: Because of increasingly stressful, dangerous and unpredictable psychiatric nursing work, psychiatric nurses have experienced higher job stress than general ward nurses. Little is known about the factors that affect the turnover intention of Chinese psychiatric nurses. Understanding the influencing factors of nurses' turnover intention will help to formulate targeted measures to stabilize psychiatric nursing teams. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE: The results showed that 70.2% of psychiatric nurses had higher turnover intention. The strong turnover intention of Chinese psychiatric nurses is a problem that needs to be considered by managers. The results showed that having more children, between 31 and 39 years old, and having a part-time job were strongly associated with turnover intention. In addition, "job stress" was also an important factor, psychiatric nurses' turnover intention decreased as their job stress level decreased. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Nursing managers should pay attention to nurses who have more children, between 31 and 39 years old, and take on part-time jobs. Additionally, nursing managers should reduce job stress and implement targeted programmes to prevent psychiatric nurses' turnover. Experience-sharing meetings and mindfulness-based stress reduction training are also useful to improve the mental health status of psychiatric nurses with great job stress. Nursing managers should arrange human resources and shifts appropriately to give nurses with more children more time with their families. Provide more development opportunities for psychiatric nurses between 31 and 39 years old. Managers explore the reasons why nurses take on part-time jobs and take targeted interventions (such as increasing income) to reduce the behaviour that happens. ABSTRACT: Introduction Nurses' turnover is the main cause of nursing shortages, greatly affected by nurses' intention to leave. Nurses' turnover rate is particularly high in psychiatric wards. Several factors influencing the turnover intention of psychiatric nurses have not been well identified in China, and the association between job stress and turnover intention is still limited. Aims To examine the relationship between job stress and turnover intention and identify the influencing factors of psychiatric nurses' turnover intention. Methods Data were collected from 2355 psychiatric Chinese nurses using a cross-sectional design with an online questionnaire investigation. Results Psychiatric nurses had higher turnover intention. Significant factors influencing their turnover intention were job stress, having more children, age between 31 and 39 years old, part-time jobs, education, income and patient-to-nurse ratio. Discussion Demographics and job-related factors should be considered when developing strategies to reduce the turnover intention of psychiatric nurses. Implications for practice Nursing managers should pay attention to nurses with higher job stress levels and different demographic characteristics. Effective measures should be taken to reduce psychiatric nurses' job stress and turnover intention, such as arranging reasonable shifts, implementing targeted family-friendly policies, increasing their occupational possibilities and promoting mental health.

Methylcyclopentadienyl Manganese Tricarbonyl Alter Behavior and Cause Ultrastructural Changes in the Substantia Nigra of Rats: Comparison with Inorganic Manganese Chloride.

The antiknock additive methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese(Mn) compound. Mn neurotoxicity caused by occupational Mn exposure (mostly inorganic MnCl2) is associated with motor and cognitive disturbances, referred to as Manganism. However, the impact of environmentally relevant Mn exposure on MMT-induced Manganism is poorly understood. In this investigation, we studied the effects of MMT on motor function and brain structure, and compared its effects with those of inorganic MnCl2. After adaptive feeding for 7 days, male and female Sprague-Dawley (SD) rats in the MMT-treated groups and positive control group were treated for 8 weeks with MMT (1, 2 and 4 mg/kg/i.g.) or MnCl2·4H2O (200 mg/kg/i.g.). Mn content in blood, liver, spleen and distinct brain regions was determined by inductively coupled plasma-mass spectrometer (ICP-MS). We found that MMT and MnCl2 exposure led to slower body-weight-gain in female rats, impaired motor and balance function and spatial learning and memory both in male and female rats. HE staining showed that MMT and MnCl2 led to altered structure of the substantia nigra pars compacta (SNpc), and Nissl staining corroborated MMT's propensity to damage the SNpc both in male and female rat. In addition, Immunostaining of the SNpc showed decreased TH-positive neurons in MMT- and MnCl2-treated rats, concomitant with Iba1 activation in microglia. Moreover, no statistically significant difference was noted between the rats in the H-MMT and MnCl2 groups. In summary, these findings suggest that MMT and MnCl2 exposure cause ultrastructural changes in the SNpc neurons culminating in altered motor behavior and cognition, suggesting that altered SNpc structure and function may underline the motor and cognitive deficits inherent to Manganism, and accounting for MMT and MnCl2's manifestations of atypical parkinsonism.

Exploring the Effectiveness and Durability of Trans-Kingdom Silencing of Fungal Genes in the Vascular Pathogen Verticillium dahliae.

Host-induced gene silencing (HIGS) based on trans-kingdom RNA interference (RNAi) has been successfully exploited to engineer host resistance to pests and pathogens, including fungi and oomycetes. However, revealing the mechanisms underlying trans-kingdom RNAi between hosts and pathogens lags behind applications. The effectiveness and durability of trans-kingdom silencing of pathogenic genes are uncharacterized. In this study, using our transgenic 35S-VdH1i cotton plants in which dsVdH1-derived small RNAs (siVdH1) accumulated, small RNA sequencing analysis revealed that siVdH1s exclusively occur within the double-stranded (ds)VdH1 region, and no transitive siRNAs were produced beyond this region in recovered hyphae of Verticillium dahliae (V. dahliae). Accordingly, we found that VdH1 silencing was reduced over time in recovered hyphae cultured in vitro, inferring that once the fungus got rid of the 35S-VdH1i cotton plants would gradually regain their pathogenicity. To explore whether continually exporting dsRNAs/siRNAs from transgenic plants into recipient fungal cells guaranteed the effectiveness and stability of HIGS, we created GFP/RFP double-labeled V. dahliae and transgenic Arabidopsis expressing dsGFP (35S-GFPi plants). Confocal images visually demonstrate the efficient silencing of GFP in V. dahliae that colonized host vascular tissues. Taken together, our results demonstrate that HIGS effectively triggers long-lasting trans-kingdom RNAi during plant vasculature V. dahliae interactions, despite no amplification or transitivity of RNAi being noted in this soil-borne fungal pathogen.

Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus†.

Bone marrow-derived progenitor cells (BMDPCs) are mobilized to the circulation in pregnancy and get recruited to the pregnant decidua where they contribute functionally to decidualization and successful implantation. However, the molecular mechanisms underlying BMDPCs recruitment to the decidua are unknown. CXCL12 ligand and its CXCR4 receptor play crucial roles in the mobilization and homing of stem/progenitor cells to various tissues. To investigate the role of CXCL12-CXCR4 axis in BMDPCs recruitment to decidua, we created transgenic GFP mice harboring CXCR4 gene susceptible to tamoxifen-inducible Cre-mediated ablation. These mice served as BM donors into wild-type C57BL/6 J female recipients using a 5-fluorouracil-based nongonadotoxic submyeloablation to achieve BM-specific CXCR4 knockout (CXCR4KO). Successful CXCR4 ablation was confirmed by RT-PCR and in vitro cell migration assays. Flow cytometry and immunohistochemistry showed a significant increase in GFP+ BM-derived cells (BMDCs) in the implantation site as compared to the nonpregnant uterus of control (2.7-fold) and CXCR4KO (1.8-fold) mice. This increase was uterus-specific and was not observed in other organs. This pregnancy-induced increase occurred in both hematopoietic (CD45+) and nonhematopoietic (CD45-) uterine BMDCs in control mice. In contrast, in CXCR4KO mice there was no increase in nonhematopoietic BMDCs in the pregnant uterus. Moreover, decidual recruitment of myeloid cells but not NK cells was diminished by BM CXCR4 deletion. Immunofluorescence showed the presence of nonhematopoietic GFP+ cells that were negative for CD45 (panleukocyte) and DBA (NK) markers in control but not CXCR4KO decidua. In conclusion, we report that CXCR4 expression in nonhematopoietic BMDPCs is essential for their recruitment to the pregnant decidua.