Correlation between PRDX2 and spermatogenesis under oxidative stress.

BACKGROUND: Obesity is one of the world's diseases that endanger human health, causing systemic inflammation caused by excessive reactive oxygen damage. An increase in the proportion of obese people with reduced sperm motility has been reported. But the mechanism behind it remains unclear. Peroxiredoxin 2 (PRDX2) is a member of the peroxidase family that effectively removes hydrogen peroxide. This study is to clarify the expression of PRDX2 in the testes of obese mice and lay a foundation for further exploration of the regulatory and protective effects of PRDX2 on spermatogenesis. METHOD: A model of high-fat-induced obesity in animals was constructed, and the expression of PRDX2 in the testes of the two groups was detected by immunohistochemistry, western blotting, immunofluorescence and other techniques. Hydrogen peroxide (H2O2) and cholesterol were co-cultured in testicular support cells for 48 h to observe the expression of PRDX2. RESULT: PRDX2 expression was reduced in the testes of the obese group, and immunohistochemistry showed that it was mainly localized to supporting cells. H2O2 inhibits the expression of PRDX2 in Sertoli cells, and high cholesterol upregulates the expression of PRDX2 in Sertoli cells. CONCLUSION: PRDX2 has some antioxidant properties against changes in the testicular environment caused by HFD. And under short-term oxidative stress to enhance its antioxidant capacity. PRDX2 may be involved in maintaining the oxidative balance of the spermatogenesis environment.

Mapping trade-offs among key ecosystem functions in tidal marsh to inform spatial management policy for exotic Spartina alterniflora.

Invasive Spartina alterniflora has become a global management challenge in coastal wetlands. China has decided to eradicate it completely, but the high costs and its provision of beneficial ecosystem functions (EF, in the form of blue carbon and coastal protection) have raised concerns about its removal. Here, using the Yangtze Estuary as a case study, we explore a reasonable pathway of S. alterniflora management that balanced control of invasive species and EF. We simulated the spatial patterns of two key EF - blue carbon storage and wave attenuation - and identified appropriate zones for eradicating S. alterniflora based on their trade-offs. We observed contrasting patterns along the land-sea gradient for S. alterniflora community, with a decrease in blue carbon storage and an increase in wave attenuation. Notably, pioneer S. alterniflora near the foreshore displayed a high cluster of blue carbon storage (63.61 ± 7.33 Mg C ha-1) and dissipated nearly 70% of wave energy by a width of 163 m. The trade-offs between the two EF indicated that the eradication project should be implemented along the seawall rather than the foreshore. Even in the scenario of prioritized shore defense with the largest eradication zone, S. alterniflora still stored 43.1% more carbon (10.67 Gg C) compared to complete eradication and dissipated over 70% of wave energy in extreme events. Our study innovatively integrates eradication and reservation in S. alterniflora management, providing a sustainable and flexible spatial strategy that meets the needs of stakeholders.

Endoplasmic reticulum stress increases exosome biogenesis and packaging relevant to sperm maturation in response to oxidative stress in obese mice.

BACKGROUND: Mammalian sperm maturation in the epididymis is mainly modulated by exosomes that are secreted into the epididymal lumen from epididymal epithelial cells (EECs). Exposure to oxidative stress (OS) resulting from being fed a high fat diet (HFD) reduces sperm fertility, which is one of the cause inducing male infertility. Thus, we hypothesize that stress-induced changes in exosome content play a critical role in mediating this detrimental process.  METHODS: An obese mouse model was established by feeding a HFD. Then oxidative stress status was measured in the mouse caput epididymis, epididymal fluid and spermatozoa. Meanwhile, epididymis-derived purified exosomes were isolated and validated. Subsequently, liquid chromatography tandem mass spectrometry (LC-MS) was used to perform proteomic analysis of purified exosomes. Gene Ontology (GO) analysis was performed along with pathway enrichment to identify differentially expressed proteins (DEPs). RESULTS: Two hundred and two DEPs mostly related to endoplasmic reticulum (ER) function were identified in the exosomes separated from the epididymis of control mice and obese mice. The ER stress and CD63 (an exosome marker), both increased in the caput epididymis of obese mice. Furthermore, an in vitro study showed that palmitic acid (PA), an-oxidative stress inducer, increased exosome biogenesis and secretion in the EECs. CONCLUSION: Oxidative stress in the epididymal microenvironment induces ER stress in the EECs. This effect alters the epididymis-derived exosome content, profile and amounts of their differentially expressed ER proteins. Such changes may affect exosome biogenesis and cargo packaging, finally leading to abnormalities in sperm maturation and fertility.

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11 C]UCB-J.

INTRODUCTION: For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy. With the recent advent of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, we have begun to evaluate the consequences of synaptic alterations in vivo. METHODS: We examined the relationship between synaptic density measured by [11 C]UCB-J PET and neuropsychological test performance in 45 participants with early AD. RESULTS: Global synaptic density showed a significant positive association with global cognition and performance on five individual cognitive domains in participants with early AD. Synaptic density was a stronger predictor of cognitive performance than gray matter volume. CONCLUSION: These results confirm neuropathologic studies demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the early stages of AD.

Ethnobotanical survey of antifertility medicinal plants in Dali District, Yunnan Province, China.

In recent years, contraceptive medication has been widely used for birth control. It is worth noting that contraceptive medication from botanical source has great potential for clinical use. Yunnan is the province with the most species of plants in China and is known as the "plant kingdom". This study aims to archive herbal remedies traditionally used as antifertility remedies in Dali District, Yunnan Province, P. R. China. The survey was conducted from February 2011 to September 2016 in the population distributed in Dali and the surrounding counties. The data were collected from three groups of practitioners within the study area: therapists using traditional medicines (n = 104), aboriginal families (n = 37), and herbalists in commercial stalls (n = 12), and a total number of 117 plant species were recorded. Among the 117 plant species, 104 of which have been authenticated by a plant taxonomist from the Dali Herbarium. These plants were classified into 98 genera and 54 families, including Leguminosae (12 species), Liliaceae (7 species), Cucurbitaceae, Rosaceae and Rutaceae (5 species, respectively), Malvaceae, Compositae and Euphorbiaceae (4 species, respectively). Our data provides an in-depth delineation of the contraceptive plants used in Dali, which serve as valuable information for the practitioners of traditional Chinese medicine in contraceptive use. In addition, these data also hint that plants from different genus contain contraceptive components, which should be avoided by pregnant women. Future studies are required to identify the active contraceptive components, assess the toxicology, and elucidate the pharmacological mechanism of action.

Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [18F]FPEB PET.

OBJECTIVE: Metabotropic glutamate receptor subtype 5 (mGluR5) is integral to the brain glutamatergic system and cognitive function. This study investigated whether aging is associated with decreased brain mGluR5 availability. METHODS: Cognitively normal participants (n = 45), aged 18 to 84 years, underwent [18F]FPEB positron emission tomography scans to quantify brain mGluR5. Distribution volume (VT) was computed using a venous or arterial input function and equilibrium modeling from 90 to 120 min. In the primary analysis, the association between age and VT in the hippocampus and association cortex was evaluated using a linear mixed model. Exploratory analyses assessed the association between age and VT in multiple brain regions. The contribution of gray matter tissue alterations and partial volume effects to associations with age was also examined. RESULTS: In the primary analysis, older age was associated with lower [18F]FPEB binding to mGluR5 (P = 0.026), whereas this association was not significant after gray matter masking or partial volume correction to account for age-related tissue loss. Post hoc analyses revealed an age-related decline in mGluR5 availability in the hippocampus of 4.5% per decade (P = 0.007) and a non-significant trend in the association cortex (P = 0.085). An exploratory analysis of multiple brain regions revealed broader inverse associations of age with mGluR5 availability, but not after partial volume correction. CONCLUSION: Reductions in mGluR5 availability with age appear to be largely mediated by tissue loss. Quantification of [18F]FPEB binding to mGluR5 may expand our understanding of age-related molecular changes and the relationship with brain tissue loss.

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

INTRODUCTION: Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density. METHODS: We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [11 C]UCB-J PET and a cerebellar reference region for calculation of the distribution volume ratio. RESULTS: We observed widespread reductions of SV2A binding in medial temporal and neocortical brain regions in early AD compared to CN participants. These reductions were largely maintained after correction for volume loss and were more extensive than decreases in gray matter volume. CONCLUSION: We were able to measure widespread synaptic loss due to AD using [11 C]UCB-J PET. Future studies will continue to evaluate the utility of SV2A PET for tracking AD progression and for monitoring potential therapies.

Functional importance of palmitoyl protein thioesterase 1 (PPT1) expression by Sertoli cells in mediating cholesterol metabolism and maintenance of sperm quality.

Sertoli cells are a type of nurse cell in the seminiferous epithelium that are crucial for sustaining spermatogenesis by extending nutritional and energy support to the developing germ cells. Dysfunction of Sertoli cells could cause disordered spermatogenesis and reduced fertility in males. In this study, we focused on the expression and function of palmitoyl protein thioesterase 1 (PPT1), a lysosomal depalmitoylating enzyme, in Sertoli cells. Here, we show that PPT1 expression in Sertoli cells is responsive to cholesterol treatment and that specific knockout of Ppt1 in Sertoli cells causes male subfertility associated with poor sperm quality and a high ratio of sperm deformity. Specifically, Ppt1 deficiency leads to poor cell variably accompanied with abnormal lysosome accumulation and increased cholesterol levels in Sertoli cells. Further, Ppt1 deficiency results in poor adhesion of developing germ cells to Sertoli cells in the seminiferous epithelium, which is likely to be responsible for the reduced male fertility as a consequence of declines in sperm count and motility as well as a high incidence of sperm head deformity. In summary, PPT1 affects sperm quality and male fertility through regulating lysosomal function and cholesterol metabolism in Sertoli cells.

Proteomic alterations underlie an association with teratozoospermia in obese mice sperm.

BACKGROUND: Obesity is a worldwide crisis impairing human health. In this condition, declines in sperm quality stem from reductions in sperm concentration, motility and increase in sperm deformity. The mechanism underlying these alterations remains largely unknown. This study, determined if obesity-associated proteomic expression patterns in mice sperm parallel those in spermatozoa obtained from obese humans. METHODS: An obese mouse model was established via feeding a high-fat diet (HFD). Histological analysis identified testicular morphology and a computer assisted semen analyzer (CASA) evaluated sperm parameters. Proteome analysis was performed using a label-free quantitative LC-MS/MS system. Western blot, immunohistochemical and immunofluorescent analyses characterized protein expression levels and localization in testis, sperm and clinical samples. RESULTS: Bodyweight gains on the HFD induced hepatic steatosis. Declines in sperm motility accompanied sperm deformity development. Differential proteomic analysis identified reduced cytoskeletal proteins, centrosome and spindle pole associated protein 1 (CSPP1) and Centrin 1 (CETN1), in sperm from obese mice. In normal weight mice, both CSPP1 and CETN1 were localized in the spermatocytes and spermatids. Their expression was appreciable in the post-acrosomal region parallel to the microtubule tracks of the manchette structure in spermatids, which affects spermatid head shaping and morphological maintenance. Moreover, CSPP1 was localized in the head-tail coupling apparatus of the mature sperm, while CETN1 expression was delimited to the post-acrosomal region within the sperm head. Importantly, sperm CSPP1 and CETN1 abundance in both the overweight and obese males decreased in comparison with that in normal weight men. CONCLUSION: These findings show that regionally distinct expression and localization of CETN1 and CSPP1 is strongly related to spermiogenesis and sperm morphology maintaining. Obesity is associated with declines in the CETN1 and CSPP1 abundance and compromise of both sperm morphology in mice and relevant clinical samples. This parallelism between altered protein expression in mice and humans suggests that these effects may contribute to poor sperm quality including increased deformity.

Palmitoyl-protein thioesterase 1 (PPT1): an obesity-induced rat testicular marker of reduced fertility.

Male obesity may lead to declines in testosterone levels, reproductive hormonal profile, and semen quantity. To assess the effects of obesity on spermatogenesis, Sprague-Dawley rats fed a high-fat diet served as a model of induced obesity. The litter sizes for females mated to obese males were significantly lower as compared to females mated with normal-diet-fed controls. Their serum high-density lipoprotein, low-density lipoprotein, cholesterol, and estradiol levels increased in obese males, but testosterone and follicle-stimulating hormone levels decreased. Testicular morphology disruptions included Sertoli-cell atrophy, disrupted tight junctions, and mitochondrial degeneration in spermatogenic cells. To further investigate the molecular mechanisms leading to high-fat-diet-induced changes, we employed testicular proteomic analysis on rats fed both types of diet. Three spots were up-regulated in rats fed a high-fat diet whereas two others were downregulated. One of the upregulated spots was palmitoyl-protein thioesterase 1 (PPT1), a lipoprotein metabolizing related enzyme localized to Sertoli cells. In a Sertoli-cell line cultured in a high-fat supplemented medium, PPT1 abundance was accompanied by increases in the endocytic vesicle-associated protein, clathrin, and decreases in the tight junctional proteins, ZO-1 and occludin. In conclusion, declines in rat male fertility induced by a high-fat diet are associated with an altered testicular protein expression pattern as well as disruption of testicular Sertoli-cell and spermatogenic-cell morphology. PPT1 expression may provide a testicular marker of reduced fertility in obese males, as increases in its expression may be detrimental to Sertoli-cell function during spermatogenesis.

NDUFA4L2 is a novel biomarker for colorectal cancer through bioinformatics analysis.

Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide. NDUFAL42 is an important mitochondrial respiratory chain subunit that plays a critical role in cellular energy metabolism. However, the role of NDUFA4L2 in CRC remains unclear. Therefore, we used the data obtained from The Cancer Genome Atlas (TCGA) database to prove the relationship between NDUFA4L2 and CRC. The expression levels of NDUFA4L2 in CRC tissues were analyzed by immunohistochemical staining of NDUFA4L2 from the HPA database. Wilcoxon rank sum test, Chi-square test, Fisher exact test and logistic regression were used to evaluate relationships between clinical-pathologic features and NDUFA4L2 expression. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of NDUFA4L2 using area under curve (AUC) score. Kaplan-Meier method and Cox regression analysis were used to evaluate factors contributing to prognosis. Gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the function of differentially expressed genes associated with NDUFA4L2. Gene set enrichment analysis (GSEA) was used to predict canonical pathways associated with NDUFA4L2.Immune infiltration analysis was performed to identify the significantly involved functions of NDUFA4L2. Protein-protein interaction (PPI) networks were established and 20 hub genes identified with Cytoscape software. Increased NDUFA4L2 expression in CRC was associated with T stage (P = .019), N stage (P < .001), Pathologic stage (P = .020), Residual tumor (P = .023), Perineural invasion (P = .039), Lymphatic invasion (P = .007), Histological type(P < .001), PFI event (P = .007) and DSS event (P = .004).ROC curve suggested the significant diagnostic and prognostic ability of NDUFA4L2 (AUC = 0.878). High NDUFA4L2 expression predicted a poorer Overall-survival (P = .021), poorer progression-free interval (P = .001), and poorer Disease Specific Survival (P = .002). GO, KEGG, GSEA and immune infiltration analysis showed that NDUFA4L2 expression was correlated with regulating the function of DNA and some types of immune infiltrating cells. NDUFA4L2 expression was significantly correlated with poor survival and immune infiltrations in CRC, and it may be a promising prognostic biomarker in CRC.

Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer's disease.

BACKGROUND: Synaptic loss is considered an early pathological event and major structural correlate of cognitive impairment in Alzheimer's disease (AD). We used principal component analysis (PCA) to identify regional patterns of covariance in synaptic density using [11C]UCB-J PET and assessed the association between principal components (PC) subject scores with cognitive performance. METHODS: [11C]UCB-J binding was measured in 45 amyloid + participants with AD and 19 amyloid- cognitively normal participants aged 55-85. A validated neuropsychological battery assessed performance across five cognitive domains. PCA was applied to the pooled sample using distribution volume ratios (DVR) standardized (z-scored) by region from 42 bilateral regions of interest (ROI). RESULTS: Parallel analysis determined three significant PCs explaining 70.2% of the total variance. PC1 was characterized by positive loadings with similar contributions across the majority of ROIs. PC2 was characterized by positive and negative loadings with strongest contributions from subcortical and parietooccipital cortical regions, respectively, while PC3 was characterized by positive and negative loadings with strongest contributions from rostral and caudal cortical regions, respectively. Within the AD group, PC1 subject scores were positively correlated with performance across all cognitive domains (Pearson r = 0.24-0.40, P = 0.06-0.006), PC2 subject scores were inversely correlated with age (Pearson r = -0.45, P = 0.002) and PC3 subject scores were significantly correlated with CDR-sb (Pearson r = 0.46, P = 0.04). No significant correlations were observed between cognitive performance and PC subject scores in CN participants. CONCLUSIONS: This data-driven approach defined specific spatial patterns of synaptic density correlated with unique participant characteristics within the AD group. Our findings reinforce synaptic density as a robust biomarker of disease presence and severity in the early stages of AD.

LncRNA DIRC1 is a novel prognostic biomarker and correlated with immune infiltrates in stomach adenocarcinoma.

The potential application value of Long non-coding RNA disrupted in renal carcinoma 1 (DIRC1) has not yet been explored, the purpose of this study was to explore the relationship between DIRC1 and stomach adenocarcinoma (STAD) based on the cancer genome atlas database. Wilcoxon rank sum test, Chi-square test, Fisher test and logistic regression were used to evaluate relationships between clinical-pathologic features and DIRC1 expression. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of DIRC1 using area under curve (AUC) score. Kaplan-Meier method was used to assess the impact of DIRC1 on prognosis and the impact of DIRC1-related hub genes on prognosis. Gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the function of differentially expressed genes associated with DIRC1. Gene set enrichment analysis (GSEA) was used to predict biological states or processes associated with DIRC1. Immune infiltration analysis was performed to identify the significantly involved functions of DIRC1. Protein-protein interaction (PPI) networks were established and 10 hub genes identified with Cytoscape software. Real time-polymerase chain reaction (RT-PCR) was used to detect the expression of DIRC1 in Gastric Cancer patients and healthy people. Increased DIRC1 expression in STAD was associated with T stage (P = .004), race (P = .045), histologic grade (P = .029) and anatomic neoplasm subdivision (P = .034). ROC curve suggested the significant diagnostic ability of DIRC1 (AUC = 0.779). High DIRC1 expression predicted a poorer Overall survival (P = .004, hazard ratio: 1.63; 95% confidence interval: 1.17-2.27; P = .034). GO and KEGG analysis demonstrated that DIRC1 is related to epidermis, collagen-containing extracellular matrix, receptor-ligand activity, protein digestion and absorption, etc. GSEA demonstrated that E2F target, G2M checkpoint, Myc target, interferon γ reaction were differentially enriched in the high DIRC1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between DIRC1 and macrophages, dendritic cells, and Th1 cells were the strongest. Coregulatory proteins were included in the PPI network, higher expressions of 4 hub genes were associated with worse prognosis in STAD. RT-PCR showed that the expression of DIRC1 in the serum of Gastric Cancer patients was higher than healthy people (P = .027). DIRC1 expression was significantly correlated with poor survival and immune infiltrations in STAD, and it may be a promising prognostic biomarker in STAD.

Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease.

Sites of early neuropathologic change provide important clues regarding the initial clinical features of Alzheimer's disease (AD). We have shown significant reductions in hippocampal synaptic density in participants with AD, consistent with the early degeneration of entorhinal cortical (ERC) cells that project to hippocampus via the perforant path. In this study, [11C]UCB-J binding to synaptic vesicle glycoprotein 2A (SV2A) and [18F]flortaucipir binding to tau were measured via PET in 10 participants with AD (5 mild cognitive impairment, 5 mild dementia) and 10 cognitively normal participants. In the overall sample, ERC tau was inversely associated with hippocampal synaptic density (r = -0.59, p = 0.009). After correction for partial volume effects, the association of ERC tau with hippocampal synaptic density was stronger in the overall sample (r = -0.61, p = 0.007) and in the AD group where the effect size was large, but not statistically significant (r = -0.58, p = 0.06). This inverse association of ERC tau and hippocampal synaptic density may reflect synaptic failure due to tau pathology in ERC neurons projecting to the hippocampus.

Association of Aß deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [11C]UCB-J.

BACKGROUND: Attempts to associate amyloid-ß (Aß) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aß plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aß reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aß deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aß deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aß accumulation) compared to those with dementia (a stage of relative Aß plateau). METHODS: We measured SV2A binding ([11C]UCB-J) and Aß deposition ([11C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aß deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aß deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches. RESULTS: We observed a significant inverse association between global Aß deposition and hippocampal SV2A binding in participants with aMCI (r = - 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = - 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aß deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aß deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aß deposition and SV2A binding in the hippocampus. CONCLUSIONS: Our findings lend support to a model in which fibrillar Aß is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aß may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aß deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers.

Downregulated microRNA-140-5p expression regulates apoptosis, migration and invasion of lung cancer cells by targeting zinc finger protein 800.

Despite advances in the diagnosis and treatment in recent years, lung cancer is still one of the primary causes of cancer-associated morbidity and mortality in globally. Abnormally expressed microRNAs (miRNAs/miRs) in tumor tissues serve vital roles in the pathological mechanism of tumors and have become prospective biomarkers for cancer diagnosis. The present study aimed to investigate the effects of the miR-140-5p/zinc finger protein 800 (ZNF800) axis in lung carcinoma, and determine its potential underlying molecular mechanisms. The degree of cell proliferation was assessed via the MTT assay, while the migratory and invasive abilities of lung cancer cells were determined via the Transwell and Matrigel assays. The expression levels of miR-140-5p and ZNF800 were detected via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that miR-140-5p expression was notably higher in normal human bronchial epithelial cells compared with the respective lung cancer cell lines, H292, PC-9, CL1-5 and H460. Furthermore, miR-140-5p expression increased in the lung cancer cells compared with the control cells following transfection with miR-140-5p mimic. Overexpressing miR-140-5p significantly suppressed the proliferative, invasive and migratory abilities of H460 and PC-9 cells, and stimulated cell apoptosis by upregulating the expression of cleaved-caspase-3. Notably, these effects were reversed following transfection with miR-140-5p inhibitor. miR-140-5p was predicted as a negative regulator of ZNF800, and ZNF800 knockdown significantly suppressed the proliferative and metastatic abilities of lung adenocarcinoma (LUAD) cells, which was comparable to the effects of miR-140-5p mimic. Taken together, these results suggest that miR-140-5p may block the malignant phenotype of LUAD by negatively regulating ZNF800 expression. Thus, the miR-140-5p/ZNF800 axis may be used as an alternative therapeutic target for lung carcinoma in general, and LUAD in particular.

Land use management based on multi-scenario allocation and trade-offs of ecosystem services in Wafangdian County, Liaoning Province, China.

Developing effective methods to coordinate the trade-offs among ecosystem services (ES) is important for achieving inclusive growth and sustainable development, and has been the focus of scholars and ecosystem managers globally. Using remote sensing and geographic information system (GIS) data, our study examined Wafangdian County of Liaoning Province as a case study to reveal the spatiotemporal evolution of four ES (food supply [FS], net primary productivity [NPP], water yield [WY], and soil conservation [SC]) and changes among their interactions. Then, an ordered weighted averaging model was introduced to simulate the optimal scenario of ES allocation. Results showed that: (1) the spatial and temporal changes in ES were significant over 14 years. All ES presented an inverted U-shaped growth curve from 2000-2014. (2) Synergies were observed within provisioning services, and there were trade-offs between provisioning services and regulating services, as well as provisioning services and supporting services. (3) The optimal scenario for Wafangdian was scenario 5 (trade-off coefficient, 0.68). The allocation of FS, NPP, WY, and SC in scenario 5 were 0.187, 0.427, 0.131, and 0.063, respectively. Implementing each ES weight of optimal scenario in land use management contributed to achieving intercoordination of ES. We propose to coordinate land and sea management to restore natural habitats that were expanded into in the high ES area. It is our anticipation that this study could provide a scientific basis for optimizing the allocation of ES and improving land use structure of coastal zones in the future.

Endocrine regulation of MFS2 by branchless controls phosphate excretion and stone formation in Drosophila renal tubules.

How inorganic phosphate (Pi) homeostasis is regulated in Drosophila is currently unknown. We here identify MFS2 as a key Pi transporter in fly renal (Malpighian) tubules. Consistent with its role in Pi excretion, we found that dietary Pi induces MFS2 expression. This results in the formation of Malpighian calcium-Pi stones, while RNAi-mediated knockdown of MFS2 increases blood (hemolymph) Pi and decreases formation of Malpighian tubule stones in flies cultured on high Pi medium. Conversely, microinjection of adults with the phosphaturic human hormone fibroblast growth factor 23 (FGF23) induces tubule expression of MFS2 and decreases blood Pi. This action of FGF23 is blocked by genetic ablation of MFS2. Furthermore, genetic overexpression of the fly FGF branchless (bnl) in the tubules induces expression of MFS2 and increases Malpighian tubule stones suggesting that bnl is the endogenous phosphaturic hormone in adult flies. Finally, genetic ablation of MFS2 increased fly life span, suggesting that Malpighian tubule stones are a key element whereby high Pi diet reduces fly longevity previously reported by us. In conclusion, MFS2 mediates excretion of Pi in Drosophila, which is as in higher species under the hormonal control of FGF-signaling.

The effects of maternal cigarette smoking on pregnancy outcomes using assisted reproduction technologies: An updated meta-analysis.

There is strong evidence indicating that smoking has negative effects on female reproductive health. Studies to investigate the effects of female smoking on IVF outcomes have been conducted by several research groups, yet the results are controversial. To evaluate the impacts of female smoking on the outcomes of assisted reproduction, a meta-analysis was performed, which included studies published in English up to September 6, 2017 from the MEDLINE, EMBASE, and Cochrane library databases. Twenty-eight studies encompassing 5009 female smokers seeking assisted reproduction and 10,078 non-smokers were used in this meta-analysis. Significant negative outcomes were detected in the female smokers compared with non-smokers including decreases in live birth rate per cycle (OR=0.52, 95% CI 0.37-0.74), in clinical pregnancy rate per cycle (OR 0.59, 95% CI 0.51-0.68), in number of retrieved oocytes (MD=-0.87, 95% CI -1.39 to -0.25), and in average fertilization rate (MD=-4.80, 95% CI -8.49 to -2.02), as well as a significantly increased miscarriage rate per pregnancy (OR=2.48, 95% CI 1.79-3.43). In conclusion, the current meta-analysis provides compelling evidence that female smoking has a significantly negative impact on the outcomes of assisted reproductive technology (ART) and strongly recommends that female smokers will greatly benefit from a smoking cessation before employing ART to become pregnant.

[Efficacy of Yunnan Baiyao as an adjuvant treatment for active ulcerative colitis: an open-label randomized controlled study].

OBJECTIVE: To investigate the efficacy of Yunnan Baiyao (YNBY)as an adjuvant treatment of active ulcerative colitis. METHODS: A total of 221 patients with active ulcerative colitis were randomized into YNBY group (78 cases) and control group (143 cases). The patients were followed up for 26 weeks and time of remission and serological data (WBC, HGB, PLT, and CRP) were recorded. RESULTS: The patients receiving YNBY as an adjuvant therapy had a median remission time of 9 weeks (95% CI: 8.293-9.707), significantly shorter than that of 13 weeks (95% CI: 11.855-14.145) in the control patients (P<0.001). According to the extent of the lesion, both YNBY group and control group were classified into E1, E2 and E3 subgroups, and the median remission time was 7 versus 11 weeks in E1 subgroups (P=0.09), 10 versus 13 weeks in E2 subgroups (P=0.04), and 9 versus 14 weeks in E3 subgroups (P<0.001). According to the disease severity, the patients in YNBY group and control group had a median remission time of 9 versus 10 weeks in mild cases (P=0.568), 9 versus 14 weeks in moderate cases (P<0.001), and 11 versus 20 weeks in severe cases (P=0.001). According to the standard treatment received, the median remission time in YNBY group and control group was 9 versus 12 weeks in those receiving mesalazine (P<0.001), 9 versus 13 weeks in those receiving corticosteroid (P=0.001), and 7 versus 14 weeks in those receiving infliximab (P=0.04). Cox proportional hazards regression analysis showed that YNBY was a protective factor for disease remission. The remission time was shortened by 2.283 times (95% CI: 1.69-3.070, P<0.001) in patients having YNBY as an adjuvant treatment compared to the control group. CONCLUSION: Patients with active ulcerative colitis can benefit from YNBY as an adjuvant treatment, which shortens the time of disease remission, relieves the symptoms and improves the quality of life of the patients.