Synergistic Role of Biofilm-Associated Genes and Efflux Pump Genes in Tigecycline Resistance of Acinetobacter baumannii.

BACKGROUND Previous research reported that the resistance mechanism of Acinetobacter baumannii resistance to tigecycline was mainly related to the overexpression of the AdeABC efflux pump system. Biofilm formation is a notable pathogenesis of A. baumannii infections and antibiotic resistance. Our study explores the latent relevance of biofilm-associated genes and efflux pump genes in A. baumannii tigecycline resistance. MATERIAL AND METHODS A total of 78 clinical samples were collected from October 2018 to October 2019. Seventy-two clinically isolated A. baumannii strains were divided into a tigecycline-resistant Acinetobacter baumannii (TR-AN) group and tigecycline-sensitive Acinetobacter baumannii (TS-AN) group by tigecycline minimum inhibitory concentration tests. The biofilm formation of the 2 groups was observed using crystal violet staining. Furthermore, biofilm-related genes and efflux pump genes were analyzed by RT-PCR. RESULTS The biofilm-forming rate of the TR-AN group was 82.2%, and that of the TS-AN group was 14.8%. The biofilm synthesis gene bfs was 91.3% positive in the TR-AN group, significantly higher than in the TS-AN group at the transcription level (P<0.05). The minimum inhibitory concentration of tigecycline was higher in the TR-AN group with biofilm formation than in the TR-AN group without biofilm formation (P<0.05). The efflux pump AdeB gene was 95.2% positive in the TR-AN group with biofilm formation and 38.7% positive in the TR-AN group without biofilm formation. CONCLUSIONS The biofilm formation of A. baumannii may be positively related to tigecycline resistance ability because of the co-expression of the bfs gene and the AdeB efflux pump gene. The enhanced transcription level of bfs and AdeB promotes biofilm formation to improve the resistance of A. baumannii to tigecycline.

Hippocampal microRNA-26a-3p deficit contributes to neuroinflammation and behavioral disorders via p38 MAPK signaling pathway in rats.

BACKGROUND: Neuronal injury is considered a critical risk factor in the pathogenesis of most neurological and neuropsychiatric diseases. However, the underlying molecular mechanisms and identification of potential therapeutic targets for preventing neuronal injury associated with brain function remain largely uncharacterized. Therefore, identifying neural mechanisms would put new insights into the progression of this condition and provide novel therapeutic strategies for the treatment of these diseases. METHODS: Stereotactic injection of AAV virus was used to knock-down the miR-26a-3p within hippocampus of rats. Behavioral changes was detected by open field test (OFT), elevated plus maze (EPM), forced swim test (FST) and sucrose preference test (SPT). The inflammatory cytokines and related proteins were verified by real-time quantitative PCR, immunoblotting or immunofluorescence assay. Golgi staining and electron microscopy analysis was used to observe the dendritic spine, synapse and ultrastructural pathology. SB203580 (0.5 mg/kg) were administered daily to prevent p38 MAPK via an intraperitoneal (i.p.) injection. Finally, electrophysiological method was used to examine the synaptic transmission via whole-cell patch-clamp recording. RESULTS: Here, we showed that miR-26a-3p deficiency within hippocampal regions leads to the activation of microglia, increased level of pro-inflammatory cytokines and behavioral disorders in rats, effects which appear to be mediated by directly targeting the p38 mitogen-activated protein kinase (MAPK)-NF-κB signaling pathway. Specifically, we found that the enhanced glia-activation may consequently result in neuronal deterioration that mainly presented as the dysregulation of structural and functional plasticity in hippocampal neurons. In contrast, preventing p38 pathway by SB203580 significantly ameliorated abnormal behavioral phenotypes and neuronal jury resulting from miR-26a-3p knock-down. CONCLUSION: These results suggest that the normal expression of miR-26a-3p exerts neuroprotective effects via suppressing neural abnormality and maintaining neuroplasticity to against behavioral disorders in rats. These effects appear to involve a down-regulation of p38 MAPK-NF-κB signaling within the hippocampal region. Taken together, these findings provide evidence that miR-26a-3p can function as a critical factor in regulating neural activity and suggest that the maintaining of normal structure and function of neurons might be a potential therapeutic strategy in the treatment of neurological disorders.

CircCERS6 Suppresses the Development of Epithelial Ovarian Cancer Through Mediating miR-630/RASSF8.

Accumulating evidence have demonstrated that circular RNAs (circRNAs) exert important roles in tumor initiation and progression. Nevertheless, the role and mechanism of circRNA ceramide synthase 6 (circCERS6) in epithelial ovarian cancer (EOC) remain to be clarified. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay, we measured RNA and protein expression. We analyzed the effects of circCERS6/microRNA-630 (miR-630)/Ras-association domain family member 8 (RASSF8) axis in cell proliferation, migration, and invasion by 5-Ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, scratch test, and transwell assay. Using RNA-pull down assay and dual-luciferase reporter assay, the interaction between miR-630 and circCERS6 or RASSF8 was verified. The in vivo role of circCERS6 in tumor growth was analyzed using xenograft mice model. CircCERS6 expression was markedly reduced in EOC tissues and cell lines. CircCERS6 overexpression hampered the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of EOC cells. CircCERS6 directly interacted with miR-630. miR-630 expression was up-regulated in EOC tissues and cell lines. CircCERS6 overexpression-induced anti-tumor effects in EOC were largely reversed by the overexpression of miR-630. RASSF8 was a direct target of miR-630. RASSF8 level was decreased in EOC tissues and cell lines. CircCERS6 up-regulated RASSF8 expression by acting as a molecular sponge for miR-630 in EOC cells. CircCERS6 overexpression-mediated suppressive effects in EOC cells were largely overturned by the silence of RASSF8. CircCERS6 overexpression blocked tumor growth in vivo. CircCERS6 overexpression hampered the proliferation, migration, invasion, and EMT of EOC cells by up-regulating RASSF8 via sponging miR-630.

Peripheral Blood Cell Ratios as Prognostic Predictors of Mortality in Patients with Hepatitis B Virus-Related Decompensated Cirrhosis.

BACKGROUND: We sought to determine the correlations between peripheral blood cell ratios (neutrophil-to-lymphocyte ratio (NLR), mean platelet volume-to-lymphocyte ratio (MPVLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white blood cell ratio (PWR)) and short-term prognosis in patients with hepatitis B virus (HBV)-associated decompensated cirrhosis (HBV-DeCi). METHODS: A total of 144 HBV-DeCi patients were enrolled. Demographic characteristics and laboratory data for the patients were acquired from their medical records. Multivariate regression analysis was applied to determine risk factors for unfavorable outcomes. The predictive performance of different ratios was examined by receiver operating characteristic curve analysis. Liver function was assessed by the Model for End-Stage Liver Disease (MELD) score. RESULTS: Twenty-one HBV-DeCi patients (14.6%) had died at 30 days. Survival was associated with lower NLR, MLR, MPVLR, and MELD score and higher PWR and PNR than non-survival. Multivariate analyses identified NLR and MELD score as independent prognostic predictors. The ability of NLR to predict mortality was higher than that of MLR, PNR, MPVLR, and PWR, but slightly lower than that of MELD score. CONCLUSIONS: The present results suggest that peripheral blood cell ratios can be useful for predicting mortality in HBV-DeCi patients. These ratios should be considered together with other measures for evaluation of prognosis in HBV-DeCi patients and are conducive to clinical practice.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

The Value of Serum Complement C1q in the Diagnosis of Acute Ischemic Stroke.

BACKGROUND: To investigate the relationship between the levels of serum complement C1q and the risk and severity of acute ischemic stroke, a total of 154 patients with acute ischemic stroke and 42 healthy volunteers as normal controls were enrolled in the present study. METHODS: According to the onset time of stroke, patients were divided into three groups. Using an immune transmission turbidity method, the levels of serum complement C1q were detected to investigate the relationship between the level of serum complement C1q and the incidence and severity of acute ischemic stroke. The risk factors of these groups were calculated using a conditional logistic regression model. The assessment of neurological function impairment was carried out according to the National Institute of Health Stroke Scale. Then correlation anal- ysis was carried out between the level of serum complement C1q among patients with acute ischemic stroke and the degree of neurological function impairment. RESULTS: The results showed that the level of serum complement C1q was higher in the ischemic stroke group than in the control group. Using a conditional logistic regression model it was discovered that serum complement C1q was the independent pathogenic factor of cerebral infarction. There also was a decreasing trend in the level of serum complement C1q with the extension of the onset time and an increasing trend in the level of serum complement C1q with the increase in the maximum diameter of infarction volume. CONCLUSIONS: Serum complement C1q is an independent risk factor for acute outbreak of ischemic stroke, whose level is closely related to the outbreak and infarct size and neurological function impairment.

Characterization of VP1 sequence of Coxsackievirus A16 isolates by Bayesian evolutionary method.

BACKGROUND: Coxsackievirus A16 (CV-A16), a major etiopathologic cause of pediatric hand, foot, and mouth disease (HFMD) worldwide, has been reported to have caused several fatalities. Revealing the evolutionary and epidemiologic dynamics of CV-A16 across time and space is central to understanding its outbreak potential. METHODS: In this study, we isolated six CV-A16 strains in China's Jilin province and construct a maximum clade credibility (MCC) tree for CV-A16 VP1 gene by the Bayesian Markov Chain Monte Carlo method using 708 strains from GenBank with epidemiological information. The evolution characteristics of CV-A16 VP1 gene was also analysed dynamicly through Bayesian skyline plot. RESULTS: All CV-A16 strains identified could be classified into five major genogroups, denoted by GI-GV. GIV and GV have co-circulated in China since 2007, and the CV-A16 epidemic strain isolated in the Jilin province, China, can be classified as GIV-3. The CV-A16 genogroups circulating recently in China have the same ancestor since 2007. The genetic diversity of the CV-A16 VP1 gene shows a continuous increase since the mid-1990s, with sharp increases in genetic diversity in 1997 and 2007 and reached peak in 2007. Very low genetic diversity existed after 2010. The CV-A16 VP1 gene evolutionary rate was 6.656E-3 substitutions per site per year. CONCLUSIONS: We predicted the dynamic phylogenetic trends, which indicate outbreak trends of CV-A16, and provide theoretical foundations for clinical prevention and treatment of HFMD which caused by a CV-A16.

Vegetation restoration improved aggregation stability and aggregated-associated carbon preservation in the karst areas of Guizhou Province, southwest China.

Background: The change in the soil carbon bank is closely related to the carbon dioxide in the atmosphere, and the vegetation litter input can change the soil organic carbon content. However, due to various factors, such as soil type, climate, and plant species, the effects of vegetation restoration on the soil vary. Currently, research on aggregate-associated carbon has focused on single vegetation and soil surface layers, and the changes in soil aggregate stability and carbon sequestration under different vegetation restoration modes and in deeper soil layers remain unclear. Therefore, this study aimed to explore the differences and relationships between stability and the carbon preservation capacity (CPC) under different vegetation restoration modes and to clarify the main influencing factors of aggregate carbon preservation. Methods: Grassland (GL), shrubland (SL), woodland (WL), and garden plots (GP) were sampled, and they were compared with farmland (FL) as the control. Soil samples of 0-40 cm were collected. The soil aggregate distribution, aggregate-associated organic carbon concentration, CPC, and stability indicators, including the mean weight diameter (MWD), fractal dimension (D), soil erodibility (K), and geometric mean diameter (GMD), were measured. Results: The results showed that at 0-40 cm, vegetation restoration significantly increased the >2 mm aggregate proportions, aggregate stability, soil organic carbon (SOC) content, CPC, and soil erosion resistance. The >2 mm fractions of the GL and SL were at a significantly greater proportion at 0-40 cm than that of the other vegetation types but the CPC was only significantly different between 0 and 10 cm when compared with the other vegetation types (P < 0.05). The >2 mm aggregates showed a significant positive correlation with the CPC, MWD, and GMD (P < 0.01), and there was a significant negative correlation with the D and K (P < 0.05). The SOC and CPC of all the vegetation types were mainly distributed in the 0.25-2 mm and <0.25 mm aggregate fractions. The MWD, GMD, SOC, and CPC all gradually decreased with increasing soil depth. Overall, the effects of vegetation recovery on soil carbon sequestration and soil stability were related to vegetation type, aggregate particle size, and soil depth, and the GL and SL restoration patterns may be more suitable in this study area. Therefore, to improve the soil quality and the sequestration of organic carbon and reduce soil erosion, the protection of vegetation should be strengthened and the policy of returning farmland to forest should be prioritized.

FBXL20 promotes synaptic impairment in depression disorder via degrading vesicle-associated proteins.

BACKGROUND: Synaptic plasticity changes in presynaptic terminals or postsynaptic membranes play a critical role in cognitive impairments and emotional disorders, but the underlying molecular mechanisms in depression remain largely unknown. METHODS: The regulation effects of F-box and leucine-rich repeat protein 20 (FBXL20), vesicular glutamate transporter 1 (VGLUT1) and vesicle-associated membrane protein 1 (VAMP1) on synaptic plasticity and depressive-like behaviors examined by proteomics analysis, viral stereotaxic injection, transmission electron microscope and biochemical methods. The glutamate release detected by fluorescent probe in cultured primary pyramidal neurons. RESULTS: We found that chronic unpredictable mild stress (CUMS) induced significant synaptic deficits within hippocampus of depressed rats, accompanied with the decreased expression of VGLUT1 and VAMP1. Moreover, knockdown of VGLUT1 or VAMP1 in hippocampal pyramidal neurons resulted in abnormal glutamatergic neurotransmitter release. In addition, we found that the E3 ubiquitin ligase FBXL20 was increased within hippocampus, which may promote ubiquitination and degradation of VGLUT1 and VAMP1, and thus resulted in the reduction of glutamatergic neurotransmitter release, the disruptions of synaptic transmission and the induction of depression-like behaviors in rats. In contrast, shRNA knockdown of FBXL20 within the hippocampus of depressed rats significantly ameliorated synaptic damage and depression-like behaviors. LIMITATION: Only one type of depression model was used in the present study, while other animal models should be used in the future to confirm the underlying mechanisms reported here. CONCLUSIONS: This study provides new insights that inhibiting FBXL20 pathway in depressed rats may be an effective strategy to rescue synaptic transmission and depression-like behaviors.

Targeting Phactr4 to rescue chronic stress-induced depression-like behavior in rats via regulating neuroinflammation and neuroplasticity.

Depression is a neuropsychiatric disorder characterized by persistent pleasure loss and behavioral despair. However, the potential mechanisms and therapeutic targets for depression treatment remain unclear. Therefore, identifying the underlying pathogenesis of depression would promote the development of novel treatment and provide effective targets for antidepressant drugs. In this study, proteomics analysis showed that the expression level of phosphatase and actin regulator 4 (Phactr4) was significantly increased in the CA1 hippocampus of depressed rats. The upregulated Phactr4 might induce dysfunction of the synaptic structure via suppressing the p-LIMK/p-Cofilin signaling pathway, and promote neuroinflammation via activating the NF-κB/NLRP3 pathway, which ultimately contributes to the pathogenesis of depression. In contrast, the downregulation of Phactr4 in hippocampal CA1 of depressed rats alleviated depression-like behaviors, along with reducing neuroinflammation and improving synaptic plasticity. In conclusion, these findings provide evidence that Phactr4 plays an important role in regulating neuroinflammatory response and impairment of synaptic plasticity, effects seem to involve in the pathogenesis of depression, and Phactr4 may serve as a potential target for antidepressant treatment.

Study on mNGS Technique in Diagnosing Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients.

Objective: To investigate the value of metagenomic Next-Generation Sequencing (mNGS) in diagnosing Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV)-infected patients. Methods: In this retrospective study, non-HIV-infected patients with PJP and those diagnosed with non-PJP from August 2022 to December 2024 were selected as subjects. The presence of Pneumocystis jirovecii (PJ) and other co-pathogens in bronchoalveolar lavage fluid (BALF) was analyzed, and the diagnostic efficacy of NGS, polymerase chain reaction (PCR) and serum 1,3-ß-D-glucan (BDG) in PJP was compared with the reference standard of clinical compound diagnosis. Results: Eighty-nine non-HIV-infected patients were recruited, with dyspnea as the primary symptom (69.66%) and solid malignant tumor as the most common underlying disease (20.22%). Taking clinical compound diagnosis as the reference standard, the sensitivity, specificity, negative predictive value and positive predictive value of mNGS were higher than those detected by PCR and serum BDG. Among 42 non-HIV-infected patients with PJP who underwent mNGS and conventional pathogen detection of BALF, 6 had simple PJ infection and 36 had combined PJ infection. The detection rate of mNGS in mixed infections was significantly higher than that of conventional pathogen detection (85.71 vs 61.70%, P = 0.012). A total of 127 pathogens were detected in BALF using mNGS, among which fungi had the highest detection rate (46.46%). The fungi, viruses and bacteria detected were mainly Pneumocystis jirovecii, human gammaherpesvirus 4 and Acinetobacter baumannii. Conclusion: mNGS is highly effective in diagnosing non-HIV-infected patients with PJP and exhibits ideal performance in the detection of co-pathogens. In addition, it has certain value for clinical diagnosis and guidance of targeted anti-infective drug treatment.

Hot spots and trends in PCI prognostic research: A bibliometric analysis with CiteSpace.

BACKGROUND: The number of patients undergoing percutaneous coronary intervention (PCI) procedures is increasing along with the number of studies involving guidelines, prognostic assessments, and cardiac rehabilitation related to PCI strategies. However, fewer studies have reported the mapping of knowledge structure and hotspot analysis in this field. Our goal was to discuss and analyze the current status, hot spots and developmental trends associated with research into the prognosis of patients undergoing PCI, and to provide reference for PCI-related research. METHODS: The Web of Science Core Collection and China Knowledge Network were searched for relevant literature from January 2003 to October 2022, and CiteSpace 6.1. R3 software was used to analyze the co-occurrence, clustering, and emerging authors, institutions, and keywords. RESULTS: A total of 2666 English and 2010 Chinese publications were included. The number of publications showed a growing trend. The author with the maximum number of articles was Xu Bo. The institutions with high productivity were Peking Union Medical College and Capital Medical University. Although the number of Chinese articles was high, the cooperation between institutions was low and the impact was small. The results of the analysis suggest a shift in the focus of keywords from coronary artery disease and PCI to studies involving the assessment and intervention of risk factors associated with poor prognosis of PCI. Traditional Chinese Medicine and anxiety represent the emerging direction of PCI prognosis. The assessment of major adverse cardiovascular events and cardiac rehabilitation require careful analysis in post-PCI research. CONCLUSION: The findings of this bibliometric study present a comprehensive and systematic overview of the PCI prognosis, based on the analysis of the current status and trends in research, which may facilitate the identification of hot topics and new directions for future research.

Bioinformatics analysis of Omp19 and Omp25 proteins for designing multi-epitope vaccines against Brucella.

Brucellosis is a zoonotic disease caused by Brucella. There is no effective vaccine against human brucellosis. Omp19 and Omp25 are the outer membrane proteins of Brucella. They are widely expressed and highly conserved in Brucella and have high immunogenicity. Herein, we aim to identify multi-epitope vaccine candidates based on Omp19 and Omp25. We analyzed the physicochemical properties and protein structure of Omp19 and Omp25, and predicted the corresponding B cell and T cell epitopes using bioinformatics analysis. Omp19 and Omp25 were composed of 177 amino acids and 213 amino acids, respectively. They were both stable hydrophilic proteins. The instability indices were 44.8 and 23, respectively. The hydrophilicity was -0.1 and -0.317, respectively. In the secondary structure of Omp19 and Omp25 proteins, the α-helix accounted for 12.43% and 23.94%, the ß-sheet was 18.64% and 23.47%, the ß-turn was 6.78% and 4.23%, and the random coil was 62.15% and 48.36%. Finally, 5 B cell epitopes, 3 Th-cell epitopes and 5 CTL cell epitopes of Omp19 protein, and 4 B cell epitopes, 3 Th-cell epitopes, and 5 CTL cell epitopes of Omp25 protein were selected as vaccine candidates. In conclusion, we obtained potential B cell and T cell epitopes of the Brucella outer membrane Omp19 and Omp25 proteins. This lays the foundation for the further design of multi-epitope vaccine of Brucella.

Ginsenoside-Rg1 synergized with voluntary running exercise protects against glial activation and dysregulation of neuronal plasticity in depression.

Depression is a common psychological disease accompanied by mental disorders and somatic symptoms. However, the underlying mechanisms regarding the pathogenesis of depression are still not clear. Neuronal damage resulting from inflammation is considered to be one of the important risk factors for depression. Ginsenoside-Rg1, a sterol extract extracted from ginseng herbs, has been shown to have neuroprotective effects against neurodegenerative diseases. Moreover, running exercise, a simple behavioral therapy, has been recently shown to have antidepressant effects. However, whether these two synergized strategies are more efficient in depression treatment, especially the neural mechanisms underlying this practical and interesting treatment is unknown. In this study, we have shown that ginsenoside-Rg1 synergized with voluntary running exercise exerts more efficiency on suppressing neuroinflammation, up-regulating expression of neurotrophic factors, and synaptic-related proteins, ameliorating neuronal structural damages than that of ginsenoside-Rg1 or voluntary exercise alone, suggesting its better neuroprotective effects. More importantly, the antidepressant-like effect of this synergistic treatment was also significantly better than either of these two treatments. These results suggest that ginsenoside-Rg1, synergized with voluntary running, may have higher efficacy in the treatment of depression through anti-inflammation and the improvement of neuroplasticity. These findings may provide a new perspective for the development of a therapeutic strategy for depression.

Levomilnacipran Improves Lipopolysaccharide-Induced Dysregulation of Synaptic Plasticity and Depression-Like Behaviors via Activating BDNF/TrkB Mediated PI3K/Akt/mTOR Signaling Pathway.

Depression is a common psychological disease with high morbidity and mortality. Recently, the involvement of synaptic plasticity in the pathogenesis of depression has shed light on the direction of developing novel antidepressants. Levomilnacipran is a newly approved medication for the treatment of adult major depressive disorder. However, the detailed mechanisms underlying its antidepressant-like effects have yet to be illuminated. In this study, we aimed to investigate the role of levomilnacipran in regulating synaptic plasticity and explore the possible molecular mechanisms of its antidepressant effects using a rat model of depression induced by lipopolysaccharide (LPS). The results demonstrated that levomilnacipran (30 mg/kg, i.p.) significantly ameliorated depression-like behaviors in rats, alleviated the dysregulation of synaptic plasticity, and suppressed neuroinflammation within hippocampus induced by LPS-treatment. Levomilnacipran increased the expression of postsynaptic dense 95 (PSD-95) and synaptophysin (Syn) and reversed the imbalance between pro- and anti-inflammatory cytokines within hippocampus of depressed rats. Additionally, levomilnacipran elevated expression level of brain-derived neurotrophic factor (BDNF), accompanied by increased tyrosine kinase B (TrkB), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR). Taken together, these results suggest that levomilnacipran may exert antidepressant effects via upregulating BDNF/TrkB mediated PI3K/Akt/mTOR signaling pathway to improve synaptic plasticity. These findings reveal potential mechanisms for the antidepressant effects of levomilnacipran and offer new insights into the treatments for depression.

Levomilnacipran ameliorates lipopolysaccharide-induced depression-like behaviors and suppressed the TLR4/Ras signaling pathway.

Levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, has been reported to have anti-depressive effects. However, the detailed mechanisms underlying these effects are still unclear. This study aimed to investigate the antidepressant mechanisms of levomilnacipran to discover new perspectives on the treatment of depression in male rats. Intraperitoneal injection of lipopolysaccharide (LPS) was used to induce depressive behaviors in rats. Activation of microglia and apoptosis of neurons verified by immunofluorescence. Inflammatory related proteins and neurotrophic related proteins were verified by immunoblotting. The mRNA expression of apoptosis markers was verified by real-time quantitative PCR. Finally, electron microscopy analysis was used to observe the ultrastructural pathology of neuron. Here, we found that the anti-depression and anti-anxiety effects of levomilnacipran in the LPS-induced rat model of depression was resulted from the suppression of neuroinflammation and neuronal apoptosis within prefrontal cortex of rats. Furthermore, we found that levomilnacipran could decrease the number of microglia and suppress its activation in prefrontal cortex of rats. This effect may be mediated by suppressing the TLR4/NF-κB and Ras/p38 signaling pathways. In addition, levomilnacipran plays a neuroprotective role by increasing the expression of neurotrophic factors. Taken together, these results suggest that levomilnacipran exerts antidepressant effects by attenuating neuroinflammation to inhibit the damage in central nervous system and plays a neuroprotective role to improve depressive behaviors. These findings suggest that suppression of neuroinflammation in prefrontal cortex could ameliorate depressive behavioral disorder of rats induced by LPS, which provided a new perspective for the treatment of depression.

[Evolution Characteristics of Soil Active Organic Carbon and Carbon Pool Management Index Under Vegetation Restoration in Karst Area].

Vegetation restoration affects the carbon cycle of terrestrial ecosystems by changing the rate of carbon input and conversion. In order to explore the evolution characteristics of soil active organic carbon components and carbon pool management index during vegetation restoration in karst areas, the soil of a grassland sequence(5, 10, 15, and 20 a), shrub sequence(5, 10, 15, and 20 a), and garden sequence(5, 10, and 15 a) in a karst area was taken as the research object, and the adjacent farmland was taken as the control(CK). The effects of different vegetation restoration years on the evolution of soil organic carbon(SOC), readily oxidizable organic carbon(ROC333, ROC167, and ROC33 were all soil active organic carbon that could be oxidized by 333, 167, and 33 mmol·L-1 KMnO4), microbial biomass carbon(MBC), dissolved organic carbon(DOC), and carbon pool management index(CPMI) were analyzed. The results showed that compared with that of CK, the average grassland, shrub, and garden SOC contents in the 0-40 cm soil layer increased by 70.77%, 114.40%, and 50.17%, respectively. In the 0-20 cm soil layer, with the increase in restoration years, the SOC content of the grassland sequence and garden sequence increased first and then decreased, and that of the shrub sequence increased first, then decreased, and then increased again. ROC333, ROC167, and ROC33 were consistent with the SOC change trend of the corresponding sequence. In the 20-40 cm soil layer, the change trend of ROC333, ROC167, and ROC33 of each sequence was inconsistent with the SOC of the corresponding sequence. In the 0-40 cm soil layer, the MBC content of the grassland sequence decreased first, then increased, and then decreased, and the maximum value of MBC in each soil layer was in G15. The shrub sequence in the 0-10 cm soil layer increased first, then decreased, and then increased, and in the 10-40 cm soil layer it increased first and then decreased. The garden sequence increased first and then decreased in the 0-30 cm soil layer and gradually increased in the 30-40 cm soil layer. Kos of the three sequences decreased first, then increased, and then decreased, whereas L and LI showed the opposite of Kos. CPI increased first and then decreased; the CPMI of the grassland and garden sequences increased first and then decreased, whereas the CPMI of the shrub sequence increased first, then decreased, and then increased again. The contents of SOC, ROC333, ROC167, ROC33, and MBC and the annual growth of Kos were shrub>grassland>orchard, and the annual growth of DOC and CPMI were orchard>grassland>shrub. The contents of SOC and its components in the three sequences decreased with the increase in soil layer and had obvious surface aggregation. Redundancy analysis showed that alkali-hydrolyzable nitrogen(AN) was the main environmental factor affecting soil active organic carbon components and soil organic carbon pool under the vegetation restoration in the karst area. In summary, soil active organic carbon components and CPMI evolved with vegetation restoration years. Different vegetation restorations could increase the content of SOC and its components in karst areas to a certain extent, and shrub restoration promotes the accumulation of SOC.

Stress-induced reduction of Na+/H+ exchanger isoform 1 promotes maladaptation of neuroplasticity and exacerbates depressive behaviors.

Major depression disorder (MDD) is a neuropsychiatric disorder characterized by abnormal neuronal activity in specific brain regions. A factor that is crucial in maintaining normal neuronal functioning is intracellular pH (pHi) homeostasis. In this study, we show that chronic stress, which induces depression-like behaviors in animal models, down-regulates the expression of the hippocampal Na+/H+ exchanger isoform 1, NHE1, a major determinant of pHi in neurons. Knockdown of NHE1 in CA1 hippocampal pyramidal neurons leads to intracellular acidification, promotes dendritic spine loss, lowers excitatory synaptic transmission, and enhances the susceptibility to stress exposure in rats. Moreover, E3 ubiquitin ligase cullin4A may promote ubiquitination and degradation of NHE1 to induce these effects of an unbalanced pHi on synaptic processes. Electrophysiological data further suggest that the abnormal excitability of hippocampal neurons caused by maladaptation of neuroplasticity may be involved in the pathogenesis of this disease. These findings elucidate a mechanism for pHi homeostasis alteration as related to MDD.

[Negative association of STAMP2 gene polymorphisms with essential hypertension in Xinjiang Uygur population].

OBJECTIVE: To investigate the relationship between the genetic polymorphisms of the six transmembrane protein of prostate 2 gene (STAMP2) and essential hypertension in Xinjiang Uygur population. METHODS: The sequences of STAMP2 gene functional region were sequenced in Xinjiang Uygur population with hypertension. The representative variations selected were genotyped by TaqMan-PCR method in 2047 Uygur individuals, including 810 patients with hypertension and 1237 healthy subjects. The association of the genetic variations of the STAMP2 gene with hypertension in Uygur was analyzed. RESULTS: In the three representative variations (rs8122, rs1981529 and rs34741656) genotyped, there were no significant differences in genotype distribution and allele frequencies between the essential hypertension and control groups (P > 0.05). In ANCOVA analysis, none of the polymorphisms was significantly associated with systolic blood pressure and diastolic blood pressure (P > 0.05). There were no significant differences in haplotype frequencies between the two groups either(P > 0.05). CONCLUSION: There was no association of the three polymorphisms (rs8122, rs1981529 and rs34741656) in the STAMP2 gene with essential hypertension in Xinjiang Uygur population.

[Genetic variation and association of STEAP4 gene with metabolic syndrome in Chinese Uygur patients].

OBJECTIVE: To investigate the genetic variations of the six transmembrane epithelial antigen of prostate 4 gene (STEAP4) in Chinese Uygur patients with metabolic syndrome (MetS) and to analyze the association of the representative genetic variations of STEAP4 gene with MetS in the population. METHODS: The sequences of STEAP4 gene functional region (all exons, exon-intron boundaries and the putative promoter region, including the -1 kb 5'and 3'untranslated regions) were amplified and sequenced for patients with MetS. The representative variations were selected based on the function (missense mutation) and linkage disequilibrxium (γ² > 0.8) and genotyped with TaqMan-PCR method in 1910 general populations (682 MetS and 1228 non-MetS controls). The subjects were selected from the cross-sectional study of obesity, hypertension, diabetes, dyslipidemia from January to February 2007 among Uygur people, a relatively isolated population with a relatively homogeneous environment, in Hextian area in Xinjiang Uygur Autonomous Region. RESULTS: (1) Fourteen novel and six known single nucleotide polymorphisms (SNPs) or mutations, including 2 missense mutations, were identified at the functional region of STEAP4 gene in 96 Uygur patients with MetS. The minor allele frequencies of the SNPs of STEAP4 gene in Uygur population were different from that in European and Chinese Han in Beijing area. (2) The SNP 364G/A (rs34741656, Ala122Thr) was significantly associated with MetS [dominant model P = 0.034, OR = 0.757(95%CI: 0.584-0.982) adjusted for age and gender], and was associated with fasting blood glucose (FBG) (P = 0.049) and 2-hour postprandial glucose (2HPG) (P = 0.027) levels in controls. In this SNP, the AA carriers had lower blood glucose levels compared with subjects carrying GG and GT genotypes. (3) The common haplotype H4 (rs8122/rs1981529/ rs34741656, G-A-A), may be associated with MetS (permutation P = 0.089). CONCLUSION: STEAP 4 genetic polymorphisms may be associated with MetS risk in Chinese Uygur population.