Maternal methylosome protein 50 is essential for embryonic development in medaka Oryzias latipes.

Methylosome protein 50 (Mep50) is a protein that is rich in WD40 domains, which mediate and regulate a variety of physiological processes in organisms. Previous studies indicated the necessity of Mep50 in embryogenesis in mice Mus musculus and fish. This study aimed to further understand the roles of maternal Mep50 in early embryogenesis using medaka Oryzias latipes as a model. Without maternal Mep50, medaka zygotes developed to the pre-early gastrula stage but died later. The transcriptome of the embryos at the pre-early gastrula stage was analyzed by RNA sequencing. The results indicated that 1572 genes were significantly upregulated and 741 genes were significantly downregulated in the embryos without maternal Mep50. In the differentially expressed genes (DEGs), the DNA-binding proteins, such as histones and members of the small chromosome maintenance complex, were enriched. The major interfered regulatory networks in the embryos losing maternal Mep50 included DNA replication and cell cycle regulation, AP-1 transcription factors such as Jun and Fos, the Wnt pathway, RNA processing, and the extracellular matrix. Quantitative RT-PCR verified 16 DEGs, including prmt5, H2A, cpsf, jun, mcm4, myc, p21, ccne2, cdk6, and col1, among others. It was speculated that the absence of maternal Mep50 could potentially lead to errors in DNA replication and cell cycle arrest, ultimately resulting in cell apoptosis. This eventually resulted in the failure of gastrulation and embryonic death. The results indicate the importance of maternal Mep50 in early embryonic development, particularly in medaka fish.

Methylosome protein 50 is necessary for oogenesis in medaka.

Methylosome protein 50 (Mep50) functions as a partner to protein arginine methyltransferase 5. MEP50 serves as a coactivator for both the androgen receptor and estrogen receptor in humans. Mep50 plays a crucial role in the development of germ cells in Drosophila. The precise role of Mep50 in oogenesis remains unclear in vertebrates. The objective of this study was to investigate the role of Mep50 in oogenesis in medaka fish. Disruption of Mep50 resulted in impaired oogenesis and the formation of multiple oocyte follicles in medaka. RNA-seq analysis revealed significant differential gene expression in the mutant ovary, with 4542 genes up-regulated and 1264 genes down-regulated. The regulated genes were found to be enriched in cellular matrices and ECM-receptor interaction, the Notch signaling pathway, the PI3K-Akt signaling pathway, the MAPK signaling pathway, the Hippo signaling pathway, and the Jak-Stat pathway, among others. In addition, the genes related to the hypothalamus-pituitary-gonad axis, steroid metabolism, and IGF system were impacted. Furthermore, the mutation of mep50 caused significant alterations in alternative splicing of pre-mRNA in ovarian cells. Quantitative RT-PCR results validated the findings from RNA-seq analysis in the specific genes, including akt2, map3k5, yap1, fshr, cyp17a, igf1, ythdc2, cdk6, and col1, among others. The findings of this study demonstrate that Mep50 plays a crucial role in oogenesis, participating in a diverse range of biological processes such as steroid metabolism, cell matrix regulation, and signal pathways. This may be achieved through the regulation of gene expression via mRNA splicing in medaka ovarian cells.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease: A literature review.

Tumor necrosis factor-α (TNF-α) antagonists, the first biologics approved for treating patients with inflammatory bowel disease (IBD), are effective for the induction and maintenance of remission and significantly improving prognosis. However, up to one-third of treated patients show primary nonresponse (PNR) to anti-TNF-α therapies, and 23%-50% of IBD patients experience loss of response (LOR) to these biologics during subsequent treatment. There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs. This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients. Most predictors remain controversial, and only previous surgical history, disease manifestations, drug concentrations, antidrug antibodies, serum albumin, some biologic markers, and some genetic markers may be potentially predictive. In addition, we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists. Therapeutic drug monitoring plays an important role in treatment selection. Dose escalation, combination therapy, switching to a different anti-TNF drug, or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

Mep50 is essential for embryonic development in medaka fish.

Mep50 as a partner promotes the activity and substrate affinity of Prmt5. Prmt5 and Mep50 function together in multiple bioprocesses of the cells. Both Prmt5 and Mep50 are necessary for maintenance of the stem cells and are indispensable in the embryogenesis in the mammals. However, the role of Mep50 is rarely studied in fish. This study was to investigate the role of Mep50 in embryonic development of medaka. Medaka mep50 was mutated by genomic editing with CRISPR-Cas9 technology. Two mutants with a deletion of 22 and 46 bp separately in mep50 caused premature stopping of translation. The homozygotes of these mutant fish were obtained by self-crossing of the heterozygotes. These homozygotic mutants could reproduce embryos but the offspring were not viable. The apoptotic cells were significantly more in the mutant embryos than that in the wild type indicated by TUNEL assay. Quantitative RT-PCR showed that the expression of oct4 and sox2 were significantly decreased, but p53 was increased in the mutant embryos. These results suggest that disruption of mep50 severely interferes with embryogenesis and mep50 is necessary for embryonic development by maintaining stem cells and repression of apoptosis in medaka.

Chemical Synthesis and Antigenic Evaluation of Inner Core Oligosaccharides from Acinetobacter baumannii Lipopolysaccharide.

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.

Differentiating thymoma, thymic carcinoma and lymphoma based on collagen fibre patterns with T2- and diffusion-weighted magnetic resonance imaging.

OBJECTIVES: The amount and distribution of intratumoural collagen fibre vary among different thymic tumours, which can be clearly detected with T2- and diffusion-weighted MR images. To explore the incidences of collagen fibre patterns (CFPs) among thymomas, thymic carcinomas and lymphomas on imaging, and to evaluate the efficacy and reproducibility of CFPs in differential diagnosis of thymic tumours. MATERIALS AND METHODS: Three hundred and ninety-eight patients with pathologically diagnosed thymoma, thymic carcinoma and lymphoma who underwent T2- and diffusion-weighted MR imaging were retrospectively enrolled. CFPs were classified into four categories: septum sign, patchy pattern, mixed pattern and no septum sign. The incidences of CFPs were compared among different thymic tumours, and the efficacy and reproducibility in differentiating the defined tumour types were analysed. RESULTS: There were significant differences in CFPs among thymomas, thymic squamous cell carcinomas (TSCCs), other thymic carcinomas and neuroendocrine tumours (OTC&NTs) and thymic lymphomas. Septum signs were found in 209 (86%) thymomas, which differed between thymomas and any other thymic neoplasms (all p < 0.005). The patchy, mixed patterns and no septum sign were mainly seen in TSCCs (80.3%), OTC&NTs (78.9%) and thymic lymphomas (56.9%), respectively. The consistency of different CFP evaluation between two readers was either good or excellent. CFPs achieved high efficacy in identifying the thymic tumours. CONCLUSION: The CFPs based on T2- and diffusion-weighted MR imaging were of great value in the differential diagnosis of thymic tumours. KEY POINTS: • Significant differences are found in intratumoural collagen fibre patterns among thymomas, thymic squamous cell carcinomas, other thymic carcinomas and neuroendocrine tumours and thymic lymphomas. • The septum sign, patchy pattern, mixed pattern and no septum sign are mainly seen in thymomas (86%), thymic squamous cell carcinomas (80.3%), other thymic carcinomas and neuroendocrine tumours (79%) and thymic lymphomas (57%), respectively. • The collagen fibre patterns have high efficacy and reproducibility in differentiating thymomas, thymic squamous cell carcinomas and thymic lymphomas.

Alternative splicing of medaka bcl6aa and its repression by Prdm1a and Prdm1b.

Bcl6 and Prdm1 (Blimp1) are a pair of transcriptional factors that repressing each other in mammals. Prdm1 represses the expression of bcl6 by binding a cis-element of the bcl6 gene in mammals. The homologs of Bcl6 and Prdm1 have been identified in teleost fish. However, whether these two factors regulate each other in the same way in fish like that in mammals is not clear. In this study, the regulation of bcl6aa by Prdm1 was investigated in medaka. The mRNA of bcl6aa has three variants (bcl6aaX1-X3) at the 5'-end by alternative splicing detected by RT-PCR. The three variants can be detected in adult tissues and developing embryos of medaka. Prdm1a and prdm1b are expressed in the tissues and embryos where and when bcl6aa is expressed. The expression of prdm1a was high while the expression of bcl6aa was low, and vice versa, detected in the spleen after stimulation with LPS or polyI:C. In vitro reporter assay indicated that bcl6aa could be directly repressed by both Prdm1a and Prdm1b in a dosage-dependent manner. After mutation of the key base, G, of all predicted binding sites in the core promoter region of bcl6aa, the repression by Prdm1a and/or Prdm1b disappeared. The binding site of Prdm1 in the bcl6aa gene is GAAAA(T/G). These results indicate that both Prdm1a and Prdm1b directly repress the expression of bcl6aa by binding their binding sites where the 5'-G is critical in medaka fish.

Identification of Blood-Based Glycolysis Gene Associated with Alzheimer's Disease by Integrated Bioinformatics Analysis.

BACKGROUND: Alzheimer's disease (AD) is one of many common neurodegenerative diseases without ideal treatment, but early detection and intervention can prevent the disease progression. OBJECTIVE: This study aimed to identify AD-related glycolysis gene for AD diagnosis and further investigation by integrated bioinformatics analysis. METHODS: 122 subjects were recruited from the affiliated hospitals of Ningbo University between 1 October 2015 and 31 December 2016. Their clinical information and methylation levels of 8 glycolysis genes were assessed. Machine learning algorithms were used to establish an AD prediction model. Receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to assess the model. An AD risk factor model was developed by SHapley Additive exPlanations (SHAP) to extract features that had important impacts on AD. Finally, gene expression of AD-related glycolysis genes were validated by AlzData. RESULTS: An AD prediction model was developed using random forest algorithm with the best average ROC_AUC (0.969544). The threshold probability of the model was positive in the range of 0∼0.9875 by DCA. Eight glycolysis genes (GAPDHS, PKLR, PFKFB3, LDHC, DLD, ALDOC, LDHB, HK3) were identified by SHAP. Five of these genes (PFKFB3, DLD, ALDOC, LDHB, LDHC) have significant differences in gene expression between AD and control groups by Alzdata, while three of the genes (HK3, ALDOC, PKLR) are related to the pathogenesis of AD. GAPDHS is involved in the regulatory network of AD risk genes. CONCLUSION: We identified 8 AD-related glycolysis genes (GAPDHS, PFKFB3, LDHC, HK3, ALDOC, LDHB, PKLR, DLD) as promising candidate biomarkers for early diagnosis of AD by integrated bioinformatics analysis. Machine learning has the advantage in identifying genes.

Dietary Selenium Deficiency Facilitated Reduced Stomatin and Phosphatidylserine Externalization, Increasing Erythrocyte Osmotic Fragility in Mice.

Selenium (Se) is an essential trace element that maintains normal physiological functions in organisms. Since the discovery of glutathione peroxidase (GSH-PX), public interest in selenoproteins has gradually increased. Based on previous studies, dietary Se maintains erythrocyte homeostasis through selenoprotein-induced mediation of redox reactions. Furthermore, both the surface phosphatidylserine (PS) and intramembrane stomatin contents can be used as indicators of erythrocyte osmotic fragility. This study focused on the mechanism by which dietary Se deficiency increases erythrocyte osmotic fragility. We fed Se-deficient grain to mice for 8 weeks to establish a Se deficiency model in mice. We measured Se levels in the blood as well as the activities of antioxidant enzymes associated with selenoproteins in a Se-deficient environment. We used Western blotting, routine blood analysis, and other methods to detect red blood cell oxidative stress levels, membrane stomatin levels, and PS externalization. Fresh blood was collected to test erythrocyte osmotic fragility. The results showed that antioxidant enzyme activity was affected by dietary Se deficiency. Oxidative stress increased lipid peroxidation and the ROS content in the blood of the mice. Under such conditions, decreased PS exposure and stomatin content in the erythrocyte membrane eventually affected the structure of the erythrocyte membrane and increased erythrocyte osmotic fragility.

[Seasonal Chemical Composition Characteristics and Source Apportionment of PM2.5 in Zhengzhou].

The aim of this study was to fully understand the pollution characteristics and sources of PM2.5 in Zhengzhou, and to investigate the differences in four seasons and between urban and suburban areas. At the Zhengzhou environmental monitoring center (urban areas) and Zhengzhou University (suburban areas), 1284 environmental PM2.5 samples were collected in the four seasons of 2018. The concentrations of nine kinds of inorganic water-soluble ions, organic carbon, elemental carbon and 27 kinds of elements, were measured by ion chromatography, carbon analyzer, and X-ray fluorescence spectrometry, respectively. Enrichment factors (EF), index of geoaccumulation (Igeo), potential ecological risk index (RI), chemical mass balance model (CMB), backward trajectory, and potential source contribution function were the methods used to study the chemical component characteristics and source differences of PM2.5 in different seasons in the urban and suburban areas of Zhengzhou. The results showed that the annual average PM2.5 concentration at the Zhengzhou environmental monitoring center and Zhengzhou University sites reached (59.7±24.0) µg·m-3 and (74.7±13.5) µg·m-3, respectively. The PM2.5 concentration at the suburban point was higher than at the urban point with the exception of winter, and the seasonal mean concentration decreased in the order of winter > autumn > spring > summer. Compared with the urban areas, the suburban areas were more affected by crustal substances in spring, and the concentrations of all components were higher in summer and autumn than the urban areas. Nevertheless, urban areas were more affected by coal burning sources and motor vehicle sources in winter. The component analysis results showed that the influences of soil dust and building dust were greater in the suburbs in spring than in the urban areas. In autumn, the suburbs were more affected by biomass sources than the urban areas, while the urban areas were more affected by building dust than were the suburbs. The concentrations of Cu, As, Zn, Pb, and Sb were strongly influenced by anthropogenic sources, and the enrichments of Zn, Cu, As, and Pb in urban areas were greater than in the suburbs. In addition, Zn, Cu, As, and Pb exhibited potential ecological risks. The outcomes of the CMB model showed that dust sources, secondary sulfate, secondary nitrate, and coal burning sources contributed significantly to PM2.5 concentrations in spring, summer, autumn and winter, respectively. The contributions of secondary pollution sources (secondary organic aerosol, secondary sulfate, and secondary nitrate) and motor vehicle sources to urban areas were higher than to suburban areas, and the influences of biomass sources in autumn and winter were significantly higher than in spring and summer and urban areas. The backward trajectory results indicated that the local PM2.5 concentration was affected by distant transmission from the northwest except in summer, was affected by neighboring provinces in the east in four seasons, and was affected by transmission from the south, with the exception of winter. Furthermore, the consequences of potential sources demonstrated that the local PM2.5 concentration was mainly affected by the potential areas in Henan province and its boundary with neighboring provinces.

[Quantification of Nitrate Sources to Groundwater in Karst Trough-valley Areas Based on Dual Stable Isotopes of δ15N-NO3- and δ18O-NO3- and the IsoSource Model].

Due to the vulnerability of karst hydrological systems, nitrate pollution in karst groundwater has become a global common and serious environmental problem. In order to ensure drinking water safety, it is very important to accurately identify groundwater nitrate sources. The groundwater hydrochemistry and δ15N-NO3- and δ18O-NO3- isotopes were analyzed in samples taken from a suburb of Chongqing:the Longfeng karst trough-valley, which is mainly affected by agricultural activities, and the Longche karst trough-valley, which is primarily affected by urbanization. The IsoSource model was then used to quantify the groundwater nitrate sources. The results showed that:① The NO3- concentration in groundwater ranged from 19.31 mg·L-1 to 37.01 mg·L-1(mean of 28.21 mg·L-1) in the Longfeng karst trough-valley, and from 2.15 mg·L-1 to 27.69 mg·L-1(mean of 10.31 mg·L-1) in the Longche karst trough-valley. The groundwater NO3- concentration exhibited an obvious seasonal variation in both valleys. ② The δ15N-NO3- and δ18O-NO3- isotopes in groundwater in the Longfeng karst trough-valley ranged from 3.29‰ to 11.03‰ (mean of 6.74‰) and 0.88‰ to 7.51‰ (mean of 3.18‰), respectively. In contrast, groundwater in the Longche karst trough-valley presented higher δ15N-NO3- and δ18O-NO3- values that ranged from 5.25‰ to 11.40‰ (mean of 7.95‰) and 2.90‰ to 19.94‰ (mean of 11.18‰), respectively. The lower values of δ15N-NO3- and δ18O-NO3- in groundwater in the Longfeng karst trough-valley suggest that groundwater NO3- was mainly sourced from agricultural N fertilizer, while the higher values of δ15N-NO3- and δ18O-NO3- in groundwater in the Longche karst trough-valley indicate that groundwater NO3- was primarily sourced from domestic sewage. Moreover, such δ15N-NO3- and δ18O-NO3- values in groundwater indicate that nitrification was the primary process for nitrogen conversion in both valleys. Meanwhile, significant seasonal differences in groundwater δ15N-NO3- and δ18O-NO3- were observed in both valleys; the δ15N-NO3- and δ18O-NO3- values were higher during the dry season (means of 8.83‰ and 2.79‰, respectively) than during the rainy season (means of 4.64‰ and 3.58‰, respectively) in the Longfeng karst trough-valley, whereas the δ15N-NO3- and δ18O-NO3- values were lower during the dry season (means of 9.79‰ and 14.56‰, respectively) than during the rainy season (means of 5.12‰ and 7.8‰, respectively) in the Longche trough-valley. This suggests that there were differences in the seasonal NO3- sources to groundwater in both valleys. During the rainy season, the groundwater NO3- concentration in the Longfeng karst trough-valley was mainly due to the nitrification of NH4+ in precipitation and fertilizer as well as organic nitrogen in soil, whereas during the dry season, the groundwater NO3- concentration primarily originated from domestic sewage. In contrast, the groundwater NO3- concentration in the Longche karst trough-valley primarily originated from domestic sewage in both seasons. ③ The results of the IsoSource model indicated that the nitrification of NH4+ from fertilizer and rainwater was the primary NO3- source to groundwater (44.63% of the total) in the Longfeng trough valley, and was followed by domestic sewage (29.5%), soil organic nitrogen (22.38%), and NO3- from rainwater and fertilizer (<10%). During the rainy season, the groundwater NO3- concentration was mainly due to the nitrification of NH4+ from fertilizer and rainwater (52.25% of the total) in Longfeng trough-valley, while groundwater NO3- concentration primarily originated from domestic sewage during the dry season (41% of the total). In contrast, the groundwater NO3- concentration was mainly from domestic sewage (36.17%) in Longche karst trough-valley, and was followed by the nitrification of NH4+ from fertilizer and rainwater (23.5%), soil organic nitrogen (22.5%), and NO3- from rainwater and fertilizer (<10%). The groundwater NO3- concentration in the Longche karst trough-valley primarily originated from domestic sewage in both seasons, and accounted for 47% and 25% during the rainy season and dry season, respectively.

Quantifying Light Response of Leaf-Scale Water-Use Efficiency and Its Interrelationships With Photosynthesis and Stomatal Conductance in C3 and C4 Species.

Light intensity (I) is the most dynamic and significant environmental variable affecting photosynthesis (A n), stomatal conductance (g s), transpiration (T r), and water-use efficiency (WUE). Currently, studies characterizing leaf-scale WUE-I responses are rare and key questions have not been answered. In particular, (1) What shape does the response function take? (2) Are there maximum intrinsic (WUEi; WUEi-max) and instantaneous WUE (WUEinst; WUEinst-max) at the corresponding saturation irradiances (I i-sat and I inst-sat)? This study developed WUEi-I and WUEinst-I models sharing the same non-asymptotic function with previously published A n-I and g s-I models. Observation-modeling intercomparison was conducted for field-grown plants of soybean (C3) and grain amaranth (C4) to assess the robustness of our models versus the non-rectangular hyperbola models (NH models). Both types of models can reproduce WUE-I curves well over light-limited range. However, at light-saturated range, NH models overestimated WUEi-max and WUEinst-max and cannot return I i-sat and I inst-sat due to its asymptotic function. Moreover, NH models cannot describe the down-regulation of WUE induced by high light, on which our models described well. The results showed that WUEi and WUEinst increased rapidly within low range of I, driven by uncoupled photosynthesis and stomatal responsiveness. Initial response rapidity of WUEi was higher than WUEinst because the greatest increase of A n and T r occurred at low g s. C4 species showed higher WUEi-max and WUEinst-max than C3 species-at similar I i-sat and I inst-sat. Our intercomparison highlighted larger discrepancy between WUEi-I and WUEinst-I responses in C3 than C4 species, quantitatively characterizing an important advantage of C4 photosynthetic pathway-higher A n gain but lower T r cost per unit of g s change. Our models can accurately return the wealth of key quantities defining species-specific WUE-I responses-besides A n-I and g s-I responses. The key advantage is its robustness in characterizing these entangled responses over a wide I range from light-limited to light-inhibitory light intensities, through adopting the same analytical framework and the explicit and consistent definitions on these responses. Our models are of significance for physiologists and modelers-and also for breeders screening for genotypes concurrently achieving maximized photosynthesis and optimized WUE.

Can the low and high b-value distribution influence the pseudodiffusion parameter derived from IVIM DWI in normal brain?

BACKGROUND: Our study aims to reveal whether the low b-values distribution, high b-values upper limit, and the number of excitation (NEX) influence the accuracy of the intravoxel incoherent motion (IVIM) parameter derived from multi-b-value diffusion-weighted imaging (DWI) in the brain. METHODS: This prospective study was approved by the local Ethics Committee and informed consent was obtained from each participant. The five consecutive multi-b DWI with different b-value protocols (0-3500 s/mm2) were performed in 22 male healthy volunteers on a 3.0-T MRI system. The IVIM parameters from normal white matter (WM) and gray matter (GM) including slow diffusion coefficient (D), fast perfusion coefficient (D*) and perfusion fraction (f) were compared for differences among defined groups with different IVIM protocols by one-way ANOVA. RESULTS: The D* and f value of WM or GM in groups with less low b-values distribution (less than or equal to 5 b-values) were significantly lower than ones in any other group with more low b-values distribution (all P <  0.05), but no significant differences among groups with more low b-values distribution (P > 0.05). In addition, no significant differences in the D, D* and f value of WM or GM were found between group with one and more NEX of low b-values distribution (all P > 0.05). IVIM parameters in normal WM and GM strongly depended on the choice of the high b-value upper limit. CONCLUSIONS: Metrics of IVIM parameters can be affected by low and high b value distribution. Eight low b-values distribution with high b-value upper limit of 800-1000 s/mm2 may be the relatively proper set when performing brain IVIM studies.

Zinc Deficiency Promoted Fibrosis via ROS and TIMP/MMPs in the Myocardium of Mice.

Zinc (Zn) is an important trace element in the body that has antioxidant effects. It has been proven that Zn deficiency can cause oxidative stress. The purpose of the present study was to clarify the effect and mechanism of Zn deficiency on myocardial fibrosis. Mice were fed with different Zn levels dietary for 9 weeks: Zn-normal group (ZnN, 34 mg Zn/kg), Zn-deficient group (ZnD, 2 mg Zn/kg), and Zn-adequate group (ZnA, 100 mg Zn/kg). We found that the Zn-deficient diet reduced the Zn concentration in myocardial tissue. Moreover, the TUNEL results demonstrated that cardiomyocytes in the ZnD group died in large numbers. Furthermore, ROS levels were significantly increased, and metallothionein (MT) expression levels decreased in the ZnD group. The results of Sirius Red staining indicated an increase in collagen in the ZnD group. Moreover, the ELISA results showed that collagen I, III, and IV and fibronectin (FN) were increased. In addition, the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) was detected by RT-qPCR. The results showed that the expression of TIMP-1 in the ZnD group was increased, while MMPs were decreased. Immunohistochemical results showed an increase in the content of α-smooth muscle actin (α-SMA), while H&E staining showed an increase in interstitial width and a decrease in the number of cardiac cells. All data suggest that Zn deficiency enhances the oxidative stress response of myocardial tissue and eventually triggers myocardial fibrosis.

[Seasonal Characteristics and Source Analysis of Water-Soluble Ions in PM2.5 of Anyang City].

We explore the characteristics and sources of water-soluble ions in aerosol fine particulate matter (PM2.5) samples collected from Anyang, China, during typical seasonal months from 2018 to 2019. Nine water-soluble ions (Na+, NH4+, K+, Mg2+, Ca2+, F-, Cl-, NO3-, and SO42-) were analyzed. The analysis of PM2.5, water-soluble ion concentration levels, anion-cation balance, nitrogen oxidation rate (NOR), sulfur oxidation rate (SOR), and ion correlation showed that the annual average concentrations of PM2.5 and water-soluble ions in Anyang were (85.81±45.43) µg·m-3 and (48.21±30.04) µg·m-3, respectively. Concentrations of ions were ranked as:NO3- > SO42- > NH4+ > Cl- > K+ > Ca2+ > Na+ > Mg2+ > F-. The annual average concentration of the sum of NH4+, NO3-, and SO42- was (42.72±27.87) µg·m-3, which accounted for 87.14% of total water-soluble ions. Moreover, NH4+ was highly related to SO42- and NO3-. The mean values of the nitrogen oxidation rate (NOR) and sulfur oxidation rate (SOR) were 0.25 and 0.37, respectively. These results suggest that these ions were the result of secondary formation. The anion-cation charge equivalent value was 0.75-0.94, which indicates that the sampled aerosols were alkaline. NH4+ mainly existed in the form of (NH4)2SO4 and NH4NO3 in spring, summer, and autumn, whereas in winter it mainly existed in the form of NH4Cl. The results of principal component analysis indicated that secondary aerosols, coal combustion, biomass burning, and dust were the main sources of the water-soluble ions in Anyang during the sampled periods.

[Analysis of Air Pollution Characteristics and Meteorological Conditions in Zhengzhou from 2014 to 2017].

Online monitoring data of atmospheric pollutants and meteorological parameters in Zhengzhou from 2014 to 2017 were collected to analyze the concentration levels, seasonal variations, and the ratio characteristics of atmospheric pollutants, as well as the effects of meteorological conditions on these pollutants. Results show that the annual average concentrations of PM2.5 and PM10 in the four years were (88±49.8), (95.8±60.2), (78.6±70.3), and (72.0±53.5) µg·m-3, and (158.5±65.3), (167.7±82.6), (144.5±91.5), and (132.7±70.3) µg·m-3, respectively, and were approximately two times higher than the grade Ⅱ annual limits set by China. Fuel combustion and the formation of secondary pollutants were the main sources of PM2.5 in Zhengzhou. Moreover, the contribution of coal combustion was found to be decreased, while that of traffic sources increased year by year. Low wind speed, high humidity, and reduced precipitation are important meteorological factors that contribute to serious air pollution. In addition, the Potential Source Contribution Function and the Concentration-Weighted Trajectory were used to analyze the potential sources, and the contribution of these sources to the distribution of PM2.5. The potential source areas of PM2.5 were mainly distributed in neighboring cities and provinces, such as Shanxi, Shaanxi, Hubei, Shandong, and Hebei. The short-distance transmission was found to contribute significantly to the mass concentration of PM2.5.

[Sources of Nitrate in Groundwater and Its Environmental Effects in Karst Trough Valleys: A Case Study of an Underground River System in the Longfeng Trough Valley, Chongqing].

Water samples from the two underground rivers (Fenghuang River and Longju River) and samples of the dry and wet deposition of atmospheric dissolved inorganic nitrogen were taken from the Longfeng karst trough valley located in the Zhongliang mountain in the suburbs of Chongqing from May 2017 to April 2018. Anions, cations, δ15 N(NO3-), δ18 O(NO3-), δ18 O(H2O), and δ13C(DIC) isotope data were used to investigate the NO3- source and its environmental effects. The results showed:① The hydrochemistry of the two underground rivers is of the type HCO3-Ca. The NO3- concentration varied from 17.58 to 32.58 mg·L-1, with an average of 24.02 mg·L-1, and was slightly higher in rainy season than the dry season, revealing that the underground rivers were polluted. ② The δ15 N(NO3-) value ranged from -3.14‰ to 12.67‰, with an average value of 7.45‰. The δ18 O(NO3-) value ranged from -0.77‰ to 12.05‰ with an average value of 2.90‰, and was higher in the dry season than the rainy season, indicating that animal excreta and domestic sewage were main NO3- sources throughout the year. In addition, rainfall, fertilizer, and soil nitrogen were the NO3- sources during the rainy season. There are no significant differences between the NO3- sources of the two underground rivers, and nitrification is the main nitrogen conversion process. ③ The molar ratio of (Ca2++Mg2+)/HCO3- varied from 0.65 to 0.82. That of the Fenghuang River was 0.75 and that of the Longju River was 0.70. The δ13C(DIC) value ranged from -12.46‰ to -9.20‰, with a mean of -11.10‰ in the Longju River and -10.72‰ in the Fenghuang River. These values indicated that the HNO3 derived from the nitrification of NH4+ was involved in the weathering of carbonate rocks. ④ HNO3 dissolved carbonate rocks and aggravated the chemical weathering of carbonate rock in the basin, contributing 8% of the DIC in groundwater, and 9% and 7% in Fenghuang River and Longju River, respectively.

Predicting pathological subtypes and stages of thymic epithelial tumors using DWI: value of combining ADC and texture parameters.

OBJECTIVES: To explore the value of combining apparent diffusion coefficients (ADC) and texture parameters from diffusion-weighted imaging (DWI) in predicting the pathological subtypes and stages of thymic epithelial tumors (TETs). METHODS: Fifty-seven patients with TETs confirmed by pathological analysis were retrospectively enrolled. ADC values and optimal texture feature parameters were compared for differences among low-risk thymoma (LRT), high-risk thymoma (HRT), and thymic carcinoma (TC) by one-way ANOVA, and between early and advanced stages of TETs were tested using the independent samples t test. Receiver operating characteristic (ROC) curve analysis was performed to determine the differentiating efficacy. RESULTS: The ADC values in LRT and HRT were significantly higher than the values in TC (p = 0.004 and 0.001, respectively), also in early stage, values were significantly higher than ones in advanced stage of TETs (p < 0.001). Among all texture parameters analyzed in order to differentiate LRT from HRT and TC, the V312 achieved higher diagnostic efficacy with an AUC of 0.875, and combination of ADC and V312 achieved the highest diagnostic efficacy with an AUC of 0.933, for differentiating the LRT from HRT and TC. Furthermore, combination of ADC and V1030 achieved a relatively high differentiating ability with an AUC of 0.772, for differentiating early from advanced stages of TETs. CONCLUSIONS: Combination of ADC and DWI texture parameters improved the differentiating ability of TET grades, which could potentially be useful in clinical practice regarding the TET evaluation before treatment. KEY POINTS: • DWI texture analysis is useful in differentiating TET subtypes and stages. • Combination of ADC and DWI texture parameters may improve the differentiating ability of TET grades. • DWI texture analysis could potentially be useful in clinical practice regarding the TET evaluation before treatment.

[Transport Pathways and Potential Sources of PM2.5 During the Winter in Zhengzhou].

In this study, meteorological and air mass concentration data of Zhengzhou from December 2017 to February 2018 (winter) were used to quantify the influence of meteorological factors on the PM. The Hybrid Single-Particle Lagrangian Integrated Trajectory model was used to analyze the 48-hour backward trajectories and the cluster method was applied to classify the airflow backward trajectory. Moreover, the potential source contribution function and concentration-weighted trajectory analysis were applied to evaluate the transport pathways and sources of PM2.5 in Zhengzhou. The results show that the heavy pollution in Zhengzhou during winter is mainly due to the low wind speed, high relative humidity, and low precipitation. The cluster analysis revealed that up to 60% of the back trajectories came from the northwest and 25.56% of the back trajectories came from the Beijing-Tianjin area. The airflow trajectories from the south and east account for 7.5% and 6.1% with higher PM2.5 concentrations. The main potential sources of PM2.5 in Zhengzhou during winter are located in Beijing-Tianjin-Hebei air pollution transmission channel cities including Jiaozuo, Kaifeng, Xinxiang, Hebi, Puyang, Anyang, Handan, and Xingtai. The adjacent provinces, including Shanxi, Hubei, and Anhui, also have great influence on the PM2.5 in Zhengzhou.