TRIM26 alleviates fatal immunopathology by regulating inflammatory neutrophil infiltration during Candida infection.

Fungal infections have emerged as a major concern among immunocompromised patients, causing approximately 2 million deaths each year worldwide. However, the regulatory mechanisms underlying antifungal immunity remain elusive and require further investigation. The E3 ligase Trim26 belongs to the tripartite motif (Trim) protein family, which is involved in various biological processes, including cell proliferation, antiviral innate immunity, and inflammatory responses. Herein, we report that Trim26 exerts protective antifungal immune functions after fungal infection. Trim26-deficient mice are more susceptible to fungemia than their wild-type counterparts. Mechanistically, Trim26 restricts inflammatory neutrophils infiltration and limits proinflammatory cytokine production, which can attenuate kidney fungal load and renal damage during Candida infection. Trim26-deficient neutrophils showed higher proinflammatory cytokine expression and impaired fungicidal activity. We further demonstrated that excessive neutrophils infiltration in the kidney was because of the increased production of chemokines CXCL1 and CXCL2, which are mainly synthesized in the macrophages or dendritic cells of Trim26-deficient mice after Candida albicans infections. Together, our study findings unraveled the vital role of Trim26 in regulating antifungal immunity through the regulation of inflammatory neutrophils infiltration and proinflammatory cytokine and chemokine expression during candidiasis.

Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease.

BACKGROUND: Myelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation. METHODS: Multidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers. RESULTS: We demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs. CONCLUSION: Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS.

Demonstration of π-π Stacking at Interfaces: Synthesis of an Indole-Modified Monodisperse Silica Microsphere SiO2@IN.

In the present study, a novel silane coupling agent, designated INSi, was synthesized via a facile synthetic route, incorporating indole-functional moieties. This agent was further employed for the surface modification of homemade silica nanomicrospheres (SMPs). The ensuing nanomicrosphere composite, denoted as SiO2@IN, exemplified pronounced interfacial π-π interactions. Optimization of the reaction conditions was conducted using the response surface optimization technique. Subsequent validation of interfacial π-π interactions was accomplished through a synergistic approach, integrating theoretical calculations and comprehensive analyses of spectral and morphological attributes exhibited by the SiO2@IN.

Nanoporous Nickel Cathode with an Electrostatic Chlorine-Resistant Surface for Industrial Seawater Electrolysis Hydrogen Production.

Seawater electrolysis presents a promising avenue for green hydrogen production toward a carbon-free society. However, the electrode materials face significant challenges including severe chlorine-induced corrosion and high reaction overpotential, resulting in low energy conversion efficiency and low current density operation. Herein, we put forward a nanoporous nickel (npNi) cathode with high chlorine corrosion resistance for energy-efficient seawater electrolysis at industrial current densities (0.4-1 A cm-2). With the merits of an electrostatic chlorine-resistant surface, modulated Ni active sites, and a robust three-dimensional open structure, the npNi electrode showed a low hydrogen evolution reaction overpotential of 310 mV and a high electricity-hydrogen conversion efficiency of 59.7% at 400 mA cm-2 in real seawater and outperformed most Ni-based seawater electrolysis cathodes in recent publications and the commercial Ni foam electrode (459 mV, 46.4%) under the same test condition. In situ electrochemical impedance spectroscopy, high-frame-rate optical microscopy, and first-principles calculation revealed that the improved corrosion resistance, enhanced intrinsic activity, and mass transfer were responsible for the lowered electrocatalytic overpotential and enhanced energy efficiency.

Patterns of antibiotic administration in Chinese neonates: results from a multi-center, point prevalence survey.

OBJECTIVES: In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization's (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China. METHODS: One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019. RESULTS: Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group. CONCLUSION: Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates.

Clinical Results of Asymmetric Blepharoplasty Plastic Repair.

OBJECTIVE: To investigate plastic surgery repair's effects and adverse reactions in the clinical therapy of asymmetric double eyelids. METHODS: All 126 sufferers who came to the hospital for asymmetric double eyelid plastic repair from January 2022 to October 2022 were selected as the research objects, and they were divided into a control group and an observation group using the random number method, with 63 cases in each group, in which sufferers in the control group underwent full incision blepharoplasty and sufferers in the observation group underwent small incision liposuction with submerged sutures. The general data, treatment results, treatment satisfaction, related surgical indicators, and frequency of adverse reactions of the 2 groups of sufferers with asymmetric double eyelid plastic repair were compared. RESULTS: It had no statistically obvious distinction between the control group and the observation group of sufferers in terms of general data such as sex, age, weight, and height (P>0.05); the total therapy efficiency of the sufferers in the observation group (95.24%) was greater than the control group (74.60%), with P value <0.05; the total treatment satisfaction of the patients in the observation group (96.83%) was significantly higher than that in the control group (76.19%), with P value <0.05; compared with the control group, patients in the observation group had shorter operative time and healing time and less intraoperative bleeding, with P value <0.05; the total frequency of adverse reactions of sufferers in the observation group (4.76%) was less than the control group (17.46%), with P value <0.05. CONCLUSION: Small incision liposuction with submerged sutures for plastic repair has significant efficacy, relatively high patient satisfaction, and low incidence of adverse reactions, in line with patient esthetic review, which has a broad clinical application prospect.

Contribution of microRNA-30d to the prevention of the thyroid cancer occurrence and progression: mechanism and implications.

Thyroid cancer is a major endocrine tumor and represents an emerging health problem worldwide. MicroRNAs (miRNAs) have been addressed to participate in the pathogenesis and progression of thyroid cancer. However, it remains largely unknown what functions miR-30d may exert on thyroid cancer. This study, herein, aimed to identify the functional significance and machinery of miR-30d in the progression of thyroid cancer. MiR-30b presented aberrant low expression and ubiquitin-specific protease 22 (USP22) exhibited aberrant high expression in thyroid cancer tissues and cells. The current study proposed the possible machinery that miR-30d could target and negatively regulate USP22. Additionally, USP22 could enhance the stability of SIRT1 by inducing deubiquitination which consequently contributed to FOXO3a deacetylation-induced PUMA repression. Responding to the gain- or loss-of-function of miR-30d and/or USP22, behaviors of thyroid cancer cells were altered. Accordingly, miR-30d inhibited proliferation and promoted apoptosis of thyroid cancer cells by suppressing USP22 through SIRT1/FOXO3a/PUMA axis. The effects of miR-30d and USP22-mediated SIRT1/FOXO3a/PUMA axis on thyroid tumorigenesis were finally validated in murine models. We ultimately confirmed the anti-proliferative and pro-apoptotic effect of miR-30d via suppressing USP22 through in vivo findings. Conclusively, our findings highlight that the occurrence and progression of thyroid cancer can be suppressed by miR-30d-mediated inhibition of USP22 via the SIRT1/FOXO3a/PUMA axis, which provides a attractive therapeutic target for thyroid cancer treatment.

Adding simultaneous integrated boost to whole brain radiation therapy improved intracranial tumour control and minimize radiation-induced brain injury risk for the treatment of brain metastases.

BACKGROUND: Brain metastases (BMs) are the most frequent intracranial tumours associated with poor clinical outcomes. Radiotherapy is essential in the treatment of these tumours, although the optimal radiation strategy remains controversial. The present study aimed to assess whether whole brain radiation therapy with a simultaneous integrated boost (WBRT + SIB) provides any therapeutic benefit over WBRT alone. METHODS: We included and retrospectively analysed 82 patients who received WBRT + SIB and 83 who received WBRT alone between January 2012 and June 2021. Intracranial progression-free survival (PFS), local tumour control (LTC), overall survival (OS), and toxicity were compared between the groups. RESULTS: Compared to WBRT alone, WBRT + SIB improved intracranial LTC and PFS, especially in the lung cancer subgroup. Patients with high graded prognostic assessment score or well-controlled extracranial disease receiving WBRT + SIB had improved intracranial PFS and LTC. Moreover, WBRT + SIB also improved the long-term intracranial tumour control of small cell lung cancer patients. When evaluating toxicity, we found that WBRT + SIB might slightly increase the risk of radiation-induced brain injury, and that the risk increased with increasing dosage. However, low-dose WBRT + SIB had a tolerable radiation-induced brain injury risk, which was lower than that in the high-dose group, while it was comparable to that in the WBRT group. CONCLUSIONS: WBRT + SIB can be an efficient therapeutic option for patients with BMs, and is associated with improved intracranial LTC and PFS. Furthermore, low-dose WBRT + SIB (biologically effective dose [BED] ≤ 56 Gy) was recommended, based on the acceptable risk of radiation-induced brain injury and satisfactory tumour control. TRIAL REGISTRATION: Retrospectively registered.

OTUD1 Regulates Antifungal Innate Immunity through Deubiquitination of CARD9.

CARD9 is an essential adaptor protein in antifungal innate immunity mediated by C-type lectin receptors. The activity of CARD9 is critically regulated by ubiquitination; however, the deubiquitinases involved in CARD9 regulation remain incompletely understood. In this study, we identified ovarian tumor deubiquitinase 1 (OTUD1) as an essential regulator of CARD9. OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathway. OTUD1 deficiency impaired CARD9-mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation. Importantly, Otud1 -/- mice were more susceptible to fungal infection than wild-type mice in vivo. Collectively, our results identify OTUD1 as an essential regulatory component for the CARD9 signaling pathway and antifungal innate immunity through deubiquitinating CARD9.

Association of greenness surrounding school with aggression among adolescents: A multi-site study in China.

Association of greenness surrounding school with aggression among adolescents was not well understood. This study aimed to investigate the associations of greenness surrounding school with adolescents' total and sub-types of aggression and explore potential mediators underlying these associations. A multi-site study of 15,301 adolescents aged 11-20 years were recruited through a multistage, random cluster sampling across 5 representative provinces in mainland China. Satellite-derived Normalized Difference Vegetation Index (NDVI) values within circular buffers of 100 m, 500 m, and 1000 m surrounding school were used to indicate the adolescents' greenness exposure. We used the Chinese version of Buss and Warren's Aggression Questionnaire to assess total and sub-types of aggression. Daily concentrations of PM2.5, and NO2 were obtained from the China High Air Pollutants datasets. Per IQR increment of NDVI 100 m and 500 m surrounding school was associated with lower odds of total aggression; odds ratio [OR] with 95% CI was 0.958 (0.926-0.990) for the 100 m buffer and 0.963 (0.932-0.996) for the 500 m buffer, respectively. Similar associations can be observed in two sub-types of aggression, including verbal (NDVI 100 m: 0.960 (0.925-0.995); NDVI500m: 0.964 (0.930-0.999)) and indirect aggression (NDVI 100 m: 0.956 (0.924-0.990); NDVI500m: 0.953 (0.921-0.986)). There were no sex and age differences in the associations of school surrounding greenness with aggression, except that the beneficial associations of greenness exposure with total aggression (0.933(0.895-0.975) vs.1.005(0.956-1.056)), physical aggression (0.971(0.925-1.019) vs.1.098(1.043-1.156)), and hostility (0.942(0.901-0.986) vs.1.016(0.965-1.069)) were greater among participants aged ≥16 years than those aged<16 years. PM2.5 (proportion mediated estimates: 0.21; 95% CI: 0.08, 0.94) and NO2 (-0.78, 95% CI: -3.22, -0.37) mediated the association of NDVI 500 m surrounding school with total aggression. Our data indicated that exposure to greenness in school surroundings was associated with reduced aggression, particularly in verbal and indirect aggression. The presence of PM2.5 and NO2 partially mediated these associations.

The role of depressive symptoms and social support in the association of internet addiction with non-suicidal self-injury among adolescents: a cohort study in China.

BACKGROUND: Both internet addiction (IA) and non-suicidal self-injury (NSSI) are major public health concerns among adolescents, however, the association between IA and NSSI was not well understood. We aimed to investigate the association between IA and NSSI within a cohort study, and explore the mediated effect of depressive symptoms and the moderating effect of social support in the association. METHODS: A total of 1530 adolescents aged 11-14 years who completed both the baseline (T1) and 14-month follow-up (T2) survey of the Chinese Adolescent Health Growth Cohort were included for the current analysis. IA, NSSI, depressive symptoms and social support were measured at T1; depressive symptoms and NSSI were measured again at T2. Structural equation models were employed to estimate the mediated effect of depressive symptoms and the moderating effect of social support in the association between IA and NSSI at T2. RESULTS: IA was independently associated with an increased risk of NSSI at T2, with the total effect of 0.113 (95%CI 0.055-0.174). Depressive symptoms mediated the association between IA and NSSI at T2, and social support moderated the indirect but not the direct effect of IA on NSSI at T2. Sex differences were found on the mediated effect of depressive symptoms and the moderated mediation effect of social support. CONCLUSIONS: Interventions that target adolescents' NSSI who also struggle with IA may need to focus on reducing depressive symptoms and elevating social support.

Acinetobacter baumannii Bacteriophage: Progress in Isolation, Genome Sequencing, Preclinical Research, and Clinical Application.

Acinetobacter baumannii (A. baumannii) is a common nosocomial pathogen associated with serious clinical challenges owing to its rapidly increasing resistance to antibiotics. Due to their high host specificity and easy access to the natural environment, bacteriophages (phages) may serve as good antibacterial agents. Phage therapy has been successfully used to treat antibiotic-resistant A. baumannii infections. As a fundamental step before phage therapy, the characterization and sequencing of A. baumannii phages have been well studied. Until October 2022, 132 A. baumannii phages have been sequenced and studied, with their genomes ranging from 4 to 234 kb, and we summarize the characterized and sequenced A. baumannii phages. This review is a current and short overview that does not go into detail on the A. baumannii phages. In addition, preclinical studies and clinical applications of A. baumannii phages are also included.

Electrochemical Quantification of Tobramycin Retention in Pseudomonas aeruginosa as Antimicrobial Susceptibility Indicator.

The emergence and spread of bacterial resistance to antibiotics has developed into one of the most challenging threats to public health. Antibiotic susceptibility tests (ASTs) for bacterial infections are now essential, because they provide guidance for physicians in the selection of antibiotics, to which bacteria will respond. Most current AST methods require long periods of time, because of bacterial growth and incubation, leading to a prolonged and overuse of broad-spectrum antibiotics. Thus, there is a growing demand for methods and technologies that enable rapid antibiotic susceptibility assessment. Due to advantages related to cost-effectiveness, rapid response time and high sensitivity, electrochemical detection methods are promising analytical tools that can successfully quantify antibiotic uptake and retention in clinically relevant bacterial strains. This study presents the electroanalytical quantification of tobramycin (TOB) retention in susceptible and resistant bacterial strains of Pseudomonas aeruginosa. The electrochemical behavior of TOB was characterized by voltammetry, identifying redox potentials, the current dependence on pH conditions, and the detection limit at unmodified glassy carbon electrodes. The presented methodology was able to distinguish between susceptible and resistant bacterial strains, and is also capable of identifying varying degrees of resistance against TOB. The presented approach detects the immediate interaction of bacteria with an antibiotic, without the need of complex and cost-intense equipment related to genomic testing methods.

C1q/tumor necrosis factor-related protein 9 protects cultured chondrocytes from IL-1ß-induced inflammatory injury by inhibiting NLRP3 inflammasome activation via the AdipoR1/AMPK axis.

C1q/tumor necrosis factor-related protein 9 (CTRP9) has been identified as a novel anti-inflammatory factor that participates in numerous pathological conditions. However, whether CTRP9 participates in the regulation of osteoarthritis has not been studied. This work sought to determine the possible role of CTRP9 in osteoarthritis using an in vitro model, namely interleukin-1ß (IL-1ß)-stimulated chondrocytes. There was a decreased level of CTRP9 in chondrocytes after IL-1ß stimulation. CTRP9 upregulation dramatically repressed IL-1ß-evoked apoptosis and inflammatory response in cultured chondrocytes. The mechanistic investigation revealed that CTRP9 overexpression restrained the activation of the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome in IL-1ß-stimulated chondrocytes via the adiponectin receptor 1 (AdipoR1)/adenosine monophosphate-activated protein kinase (AMPK) axis. Notably, inhibition of AdipoR1 or AMPK abolished the regulatory effects of CTRP9 overexpression on IL-1ß-evoked apoptosis and inflammasome activation. Overall, the results of this work delineate that CTRP9 protects cultured chondrocytes from IL-1ß-induced inflammatory injury by inhibiting NLRP3 inflammasome activation via the AdipoR1/AMPK axis. This work underscores a potential role of CTRP9 in the progression of osteoarthritis.

Supplementary Bovine Colostrum Feedings to Formula-Fed Preterm Pigs Improve Gut Function and Reduce Necrotizing Enterocolitis.

OBJECTIVES: Exclusive feeding with bovine colostrum (BC) protects preterm pigs against necrotizing enterocolitis (NEC) and BC has recently been tested as a supplement to a mother's own milk or formula (FOR) for very preterm infants. Using preterm pigs as a model for infants, we investigated if BC has gut- and NEC-protective effects at different proportions of the daily enteral intake given as BC. METHODS: Sixty-eight caesarean-delivered preterm piglets (90% gestation) were allocated into four groups with increasing proportions of eight daily bolus feedings as BC: BC00 (only FOR feeding), BC25 (25% BC), BC50 (50% BC), or BC75 (75% BC). On day 5, the gut was collected for biochemical analyses. RESULTS: Body growth was increased in BC50 and BC75 piglets (2-fold, P < 0.05 vs BC00). The incidence of mild NEC-like lesions was similar among groups (67-86%), but BC75 reduced severe NEC-like lesions (27% vs 79% in BC00, P < 0.05). BC50 and BC75 improved hexose absorption and mucosal structure and reduced gut permeability (P < 0.05 vs BC00), while enzyme activities (lactase, aminopeptidase N and A, dipeptidyl peptidase IV) were improved in all pigs fed BC (P < 0.05). Across the measured variables, beneficial effects were most clear for the BC75 group, including reductions in colon tissue cytokine levels (interleukin 8, interleukin 1ß, tumor necrosis factor α) and expression of immune- and apoptosis-related genes (LBP, TLR4, TLR2, IL8, STAT3, IL17, C3, all P < 0.05, relative to BC00). CONCLUSION: A proportion of 50-75% of daily enteral intake as BC is required to improve the intestinal structure, function, immunology, and NEC resistance in preterm piglets also fed formula. Further studies are required to show if and how supplementary BC may support gut development in preterm infants during the immediate postnatal period. It is challenging to translate results on optimal feeding regimens between species, and preterm infants would not receive a majority of their daily enteral intake as BC.

Single-course antenatal corticosteroids is related to faster growth in very-low-birth-weight infant.

BACKGROUND: Antenatal corticosteroids (ACS) treatment is critical to support survival and lung maturation in preterm infants, however, its effect on feeding and growth is unclear. Prior preterm delivery, it remains uncertain whether ACS treatment should be continued if possible (repeated course ACS), until a certain gestational age is reached. We hypothesized that the association of single-course ACS with feeding competence and postnatal growth outcomes might be different from that of repeated course ACS in very-low-birth-weight preterm infants. METHODS: A multicenter retrospective cohort study was conducted in very-low-birth-weight preterm infants born at 23-37 weeks' gestation in South China from 2011 to 2014. Data on growth, nutritional and clinical outcomes were collected. Repeated course ACS was defined in this study as two or more courses ACS (more than single-course). Infants were stratified by gestational age (GA), including GA < 28 weeks, 28 weeks ≤ GA < 32 weeks and 32 weeks ≤ GA < 37 weeks. Multiple linear regression and multilevel model were applied to analyze the association of ACS with feeding and growth outcomes. RESULTS: A total of 841 infants were recruited. The results, just in very-low-birth-weight preterm infants born at 28-32 weeks' gestation, showed both single and repeated course of ACS regimens had shorter intubated ventilation time compared to non-ACS regimen. Single-course ACS promoted the earlier application of amino acid and enteral nutrition, and higher rate of weight increase (15.71; 95%CI 5.54-25.88) than non-ACS after adjusting for potential confounding factors. No associations of repeated course ACS with feeding, mean weight and weight increase rate were observed. CONCLUSIONS: Single-course ACS was positively related to feeding and growth outcomes in very-low-birth-weight preterm infants born at 28-32 weeks' gestation. However, the similar phenomenon was not observed in the repeated course of ACS regimen.

Moesin as a prognostic indicator of lung adenocarcinoma improves prognosis by enhancing immune lymphocyte infiltration.

BACKGROUND: Ezrin-radixin-moesin (ERM) have been explored in many cancer processes. Moesin, as its component, has also been found to play an important role in the prognosis of cancer patients, tumor metastasis, drug resistance, and others. Especially in regulating the immunity, but most results came from direct studies on immune cells, there is no clear conclusion on whether moesin has similar effects in tumor cells. And moesin has certain research results in many cancers in other aspects, but there are few about moesin in lung adenocarcinoma (LUAD). METHODS: We detect the expression of moesin in 82 LUAD and matched normal tissue samples by immunohistochemistry. Besides, for the pathological feature, we did a detailed statistical analysis. And with the help of various databases, we have done in-depth exploration of moesin's ability to enhance the extent of immune lymphocyte infiltration. RESULTS: Moesin is a poor expression in lung cancer tissues than the corresponding normal samples. And this phenomenon had a strongly associated with the prognosis and TNM stage of these LUAD patients. Moesin can enhance the infiltration of multiple immune lymphocytes in lung cancer. And this may be related to the interaction between moesin and various inflammatory molecules. CONCLUSIONS: Moesin is a newly index for the prognosis of LUAD and improves the prognosis of LUAD patients by regulating a variety of inflammation-related molecules to enhance immune lymphocytes infiltration.

NAC antagonizes arsenic-induced neurotoxicity through TMEM179 by inhibiting oxidative stress in Oli-neu cells.

Arsenic is one of the most common environmental pollutants. Neurotoxicity induced by arsenic has become a major public health concern. However, the effects of arsenic-induced neurotoxicity in the brain and the underlying molecular mechanisms are not well understood. N-acetyl-cysteine (NAC) is a thiol-based antioxidant that can antagonize heavy metal-induced neurotoxicity by scavenging reactive oxygen species (ROS). Here, we used the mouse oligodendrocyte precursor cell (OPC) line Oli-neu to explore the neurotoxic effects of arsenic and the protective effects of NAC. We found that arsenic exposure decreased cell viability, increased oxidative stress, caused mitochondrial dysfunction, and led to apoptosis of Oli-neu cells. Furthermore, we revealed that NAC treatment reversed these neurotoxic effects of arsenic. TMEM179, a key membrane protein, was found highly expressed in OPCs and to be an important factor in maintaining mitochondrial functions. We found that TMEM179 played a critical role in mediating the neurotoxic effects of arsenic and the protective role of NAC. PKCß is a downstream factor through which TMEM179 regulates the expression of apoptosis-related proteins. This study improves our understanding of the neurotoxic effects and mechanisms of arsenic exposure and the protective effects of NAC. It also identifies a potential molecular target, TMEM179, for the treatment of arsenic-induced neurotoxicity.

Seasonal and spatial variations in the phytoplankton community and their correlation with environmental factors in the Jinjiang River Estuary in Quanzhou, China.

The seasonal and spatial variation in the phytoplankton community structure and the environmental variables were investigated in December (the dry season) 2016 and July (the rainy season) 2017 in the Jinjiang River Estuary, China. We identified a total of 138 species of phytoplankton, which were mainly Chlorophyta, Bacillariophyta, and Cryptophyta in the dry season; however, in the rainy season, only Bacillariophyta were found. In the Jinjiang River Estuary, the species evenness and the biodiversity index were higher in the rainy season and that the species diversity was higher in the dry season. Redundancy analysis (RDA) revealed that the dominant species were statistically related to many of the environmental variables, including the water temperature (WT), pH, salinity (Sal), dissolved oxygen (DO), total phosphorus (TP), and total nitrogen (TN). Among the variables, the Sal, DO, TP, and TN had a significant influence on the dominant species distribution, and the WT and pH also affected the dominant species distribution to some extent.

MexXY RND pump of Pseudomonas aeruginosa PA7 effluxes bi-anionic ß-lactams carbenicillin and sulbenicillin when it partners with the outer membrane factor OprA but not with OprM.

Antibiotic resistance in Pseudomonas aeruginosa is a serious concern in healthcare systems. Among the determinants of antibiotic resistance in P. aeruginosa, efflux pumps belonging to the resistance-nodulation-division (RND) family confer resistance to a broad range of antibacterial compounds. The MexXY efflux system is widely overexpressed in P. aeruginosa isolates from cystic fibrosis (CF) patients. MexXY can form functional complexes with two different outer membrane factors (OMFs), OprA and OprM. In this study, using state-of-the-art genetic tools, the substrate specificities of MexXY-OprA and MexXY-OprM complexes were determined. Our results show, for the first time, that the substrate profile of the MexXY system from P. aeruginosa PA7 can vary depending on which OM factor (OprM or OprA) it complexes with. While both MexXY-OprA and MexXY-OprM complexes are capable of effluxing aminoglycosides, the bi-anionic ß-lactam molecules carbenicillin and sulbenicillin were found to only be the substrate of MexXY-OprA. Our study therefore shows that by partnering with different OMF proteins MexY can expand its substrate profile.