Seipin Deficiency Leads to Energy Dyshomeostasis via Inducing Hypothalamic Neuroinflammation and Aberrant Expression of Neuropeptides.

Seipin is a key regulator of lipid metabolism, the deficiency of which leads to severe lipodystrophy. Hypothalamus is the pivotal center of brain that modulates appetite and energy homeostasis, where Seipin is abundantly expressed. Whether and how Seipin deficiency leads to systemic metabolic disorders via hypothalamus-involved energy metabolism dysregulation remains to be elucidated. In the present study, we demonstrated that Seipin-deficiency induced hypothalamic inflammation, reduction of anorexigenic pro-opiomelanocortin (POMC), and elevation of orexigenic agonist-related peptide (AgRP). Importantly, administration of rosiglitazone, a thiazolidinedione antidiabetic agent, rescued POMC and AgRP expression, suppressed hypothalamic inflammation, and restored energy homeostasis in Seipin knockout mice. Our findings offer crucial insights into the mechanism of Seipin deficiency-associated energy imbalance and indicates that rosiglitazone could serve as potential intervening agent towards metabolic disorders linked to Seipin.

Seipin deficiency-induced lipid dysregulation leads to hypomyelination-associated cognitive deficits via compromising oligodendrocyte precursor cell differentiation.

Seipin is one key mediator of lipid metabolism that is highly expressed in adipose tissues as well as in the brain. Lack of Seipin gene, Bscl2, leads to not only severe lipid metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly of lipids, facilitates nerve transmission and is important for motor coordination and learning. Whether Seipin deficiency-leaded defects in learning and motor coordination is underlined by lipid dysregulation and its consequent myelin abnormalities remains to be elucidated. In the present study, we verified the expression of Seipin in oligodendrocytes (OLs) and their precursors, oligodendrocyte precursor cells (OPCs), and demonstrated that Seipin deficiency compromised OPC differentiation, which led to decreased OL numbers, myelin protein, myelinated fiber proportion and thickness of myelin. Deficiency of Seipin resulted in impaired spatial cognition and motor coordination in mice. Mechanistically, Seipin deficiency suppressed sphingolipid metabolism-related genes in OPCs and caused morphological abnormalities in lipid droplets (LDs), which markedly impeded OPC differentiation. Importantly, rosiglitazone, one agonist of PPAR-gamma, substantially restored phenotypes resulting from Seipin deficiency, such as aberrant LDs, reduced sphingolipids, obstructed OPC differentiation, and neurobehavioral defects. Collectively, the present study elucidated how Seipin deficiency-induced lipid dysregulation leads to neurobehavioral deficits via impairing myelination, which may pave the way for developing novel intervention strategy for treating metabolism-involved neurological disorders.

Mutation landscape in Chinese nodal diffuse large B-cell lymphoma by targeted next generation sequencing and their relationship with clinicopathological characteristics.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL), an aggressive and heterogenic malignant entity, is still a challenging clinical problem, since around one-third of patients are not cured with primary treatment. Next-generation sequencing (NGS) technologies have revealed common genetic mutations in DLBCL. We devised an NGS multi-gene panel to discover genetic features of Chinese nodal DLBCL patients and provide reference information for panel-based NGS detection in clinical laboratories. METHODS: A panel of 116 DLBCL genes was designed based on the literature and related databases. We analyzed 96 Chinese nodal DLBCL biopsy specimens through targeted sequencing. RESULTS: The most frequently mutated genes were KMT2D (30%), PIM1 (26%), SOCS1 (24%), MYD88 (21%), BTG1 (20%), HIST1H1E (18%), CD79B (18%), SPEN (17%), and KMT2C (16%). SPEN (17%) and DDX3X (6%) mutations were highly prevalent in our study than in Western studies. Thirty-three patients (34%) were assigned as genetic classification by the LymphGen algorithm, including 12 cases MCD, five BN2, seven EZB, seven ST2, and two EZB/ST2 complex. MYD88 L265P mutation, TP53 and BCL2 pathogenic mutations were unfavorable prognostic biomarkers in DLBCL. CONCLUSIONS: This study presents the mutation landscape in Chinese nodal DLBCL, highlights the genetic heterogeneity of DLBCL and shows the role of panel-based NGS to prediction of prognosis and potential molecular targeted therapy in DLBCL. More precise genetic classification needs further investigations.

Multi-Omics Analysis of the Effects of Soil Amendment on Rapeseed (Brassica napus L.) Photosynthesis under Drip Irrigation with Brackish Water.

Drip irrigation with brackish water increases the risk of soil salinization while alleviating water shortage in arid areas. In order to alleviate soil salinity stress on crops, polymer soil amendments are increasingly used. But the regulation mechanism of a polymer soil amendment composed of polyacrylamide polyvinyl alcohol, and manganese sulfate (PPM) on rapeseed photosynthesis under drip irrigation with different types of brackish water is still unclear. In this field study, PPM was applied to study the responses of the rapeseed (Brassica napus L.) phenotype, photosynthetic physiology, transcriptomics, and metabolomics at the peak flowering stage under drip irrigation with water containing 6 g·L-1 NaCl (S) and Na2CO3 (A). The results showed that the inhibitory effect of the A treatment on rapeseed photosynthesis was greater than that of the S treatment, which was reflected in the higher Na+ content (73.30%) and lower photosynthetic-fluorescence parameters (6.30-61.54%) and antioxidant enzyme activity (53.13-77.10%) of the A-treated plants. The application of PPM increased the biomass (63.03-75.91%), photosynthetic parameters (10.55-34.06%), chlorophyll fluorescence parameters (33.83-62.52%), leaf pigment content (10.30-187.73%), and antioxidant enzyme activity (28.37-198.57%) under S and A treatments. However, the difference is that under the S treatment, PPM regulated the sulfur metabolism, carbon fixation and carbon metabolism pathways in rapeseed leaves. And it also regulated the photosynthesis-, oxidative phosphorylation-, and TCA cycle-related metabolic pathways in rapeseed leaves under A treatment. This study will provide new insights for the application of polymer materials to tackle the salinity stress on crops caused by drip irrigation with brackish water, and solve the difficulty in brackish water utilization.

Morphological and phylogenetic analyses reveal three new species of Fusarium (Hypocreales, Nectriaceae) associated with leaf blight on Cunninghamialanceolata in China.

Chinese fir (Cunninghamialanceolata) is a special fast-growing commercial tree species in China with high economic value. In recent years, leaf blight disease on C.lanceolata has been observed frequently. The diversity of Fusarium species associated with leaf blight on C.lanceolata in China (Fujian, Guangxi, Guizhou, and Hunan provinces) was evaluated using morphological study and molecular multi-locus analyses based on RNA polymerase second largest subunit (RPB2), translation elongation factor 1-alpha (TEF-1α), and RNA polymerase largest subunit (RPB1) genes/region as well as the pairwise homoplasy index tests. A total of five Fusarium species belonging to four Fusarium species complexes were recognized in this study. Two known species including Fusariumconcentricum and F.fujikuroi belonged to the F.fujikuroi species complex, and three new Fusarium species were described, i.e., F.fujianense belonged to the F.lateritium species complex, F.guizhouense belonged to the F.sambucinum species complex, and F.hunanense belonged to the F.solani species complex. To prove Koch's postulates, pathogenicity tests on C.lanceolata revealed a wide variation in pathogenicity and aggressiveness among the species, of which F.hunanense HN33-8-2 caused the most severe symptoms and F.fujianense LC14 led to the least severe symptoms. To our knowledge, this study also represented the first report of F.concentricum, F.fujianense, F.fujikuroi, F.guizhouense, and F.hunanense causing leaf blight on C.lanceolata in China.

Seven new species of Alternaria (Pleosporales, Pleosporaceae) associated with Chinese fir, based on morphological and molecular evidence.

Chinese fir (Cunninghamialanceolata) is a special fast-growing commercial tree species in China and has significant ecological and economic value. However, it experienced damage from leaf blight caused by pathogenic fungi of the genus Alternaria. To determine the diversity of Alternaria species associated with leaf blight of Chinese fir in China, infected leaves were collected from five major cultivation provinces (Fujian, Henan, Hunan, Jiangsu and Shandong provinces). A total of 48 fungal strains of Alternaria were obtained. Comparison of morphology and phylogenetic analyses, based on nine loci (ITS, SSU, LSU, GAPDH, RPB2, TEF1, Alt a1, endoPG and OPA10-2) of the representative isolates as well as the pairwise homoplasy index tests, revealed that the fungal strains belonged to seven undescribed taxa of Alternaria, which are described here and named as Alternariacunninghamiicolasp. nov., A.dongshanqiaoensissp. nov., A.hunanensissp. nov., A.kunyuensissp. nov., А. longqiaoensissp. nov., A.shandongensissp. nov. and A.xinyangensissp. nov. In order to prove Koch's postulates, pathogenicity tests on detached Chinese fir leaves revealed significant pathogenicity amongst these species, of which A.hunanensis is the most pathogenic to Chinese fir. This study represents the first report of A.cunninghamiicola, A.dongshanqiaoensis, A.hunanensis, A.kunyuensis, A.longqiaoensis, A.shandongensis and A.xinyangensis causing leaf blight on Chinese fir. Knowledge obtained in this study enhanced our understanding of Alternaria species causing leaf blight on Chinese fir and was crucial for the disease management and the further studies in the future.

Overexpression of PtoMYB99 diminishes poplar tolerance to osmotic stress by suppressing ABA and JA biosynthesis.

Drought poses a serious challenge to sustained plant growth and crop yields in the context of global climate change. Drought tolerance in poplars and their underlying mechanisms still remain largely unknown. In this article, we investigated the overexpression of PtoMYB99 - both a drought and abscisic acid (ABA) induced gene constraining drought tolerance in poplars (as compared with wild type poplars). First, we found that PtoMYB99-OE lines exhibited increased stomatal opening and conductance, higher transpiration and photosynthetic rates, as well as reduced levels of ABA and jasmonic acid (JA). Second, PtoMYB99-OE lines accumulated more reactive oxygen species (ROS), including H2O2 and O2-, as well as malonaldehyde (MDA), proline, and soluble sugar under osmotic stress; conversely, the activity of antioxidant enzymes (SOD, POD, and CAT), was weakened in the PtoMYB99-OE lines. Third, the expression of ABA biosynthetic genes, PtoNCED3.1 and PtoNCED3.2, as well as JA biosynthetic genes, PtoOPR3.1 and PtoOPR3.2, was significantly reduced in the PtoMYB99-OE lines under both normal conditions and osmotic stress. Based on our results, we conclude that the overexpression of PtoMYB99 compromises tolerance to osmotic stress in poplar. These findings contribute to the understanding of the role of the MYB genes in drought stress and the biosynthesis of ABA and JA.

Lower PTEN may be associated with CD8+ T cell exhaustion in diffuse large B-cell lymphoma.

Initially discovered in chronic viral infection and then extended to tumor, 'T-cell exhaustion' is a broad term describing the response of T cells to chronic antigen stimulation. By definition, whether T-cell exhaustion occurs in diffuse large B-cell lymphoma (DLBCL) remains largely unknown because little has been described. Here, the immune-suppressing checkpoint molecules involved in T-cell exhaustion, including PD-1, PD-L1, TIM-3 and TIGIT, whose expression levels were analyzed in DLBCL, were retrieved from the GEPIA database. Compared with the normal control, CD8A, TNFA, IFNG and GZMA were markedly elevated in DLBCL, indicating that infiltrated CD8+ T cells predominate in DLBCL. Meanwhile, inhibitory immune checkpoints, such as PD-1, PD-L1, TIGIT and TIM-3 were drastically higher in DLBCL. PTEN, WNT2 and DKK3 expression were also appraised. It was revealed that PTEN was lower in DLBCL, without being statistically significant. In contrast with PTEN, DKK3 and WNT2 were shown to be pronouncedly higher in DLBCL relative to the normal control. Prognostically, only TIGIT was found to be associated with overall survival in DLBCL. Collectively, all the data we curetted from the GEPIA and TIMER 2.0 databases explicitly indicate that CD8+ T cell exhaustion took place, which may be linked with lower PTEN in DLBCL. To the best of our knowledge, this is the first bioinformatic report explicitly proposing that CD8+ T cell exhaustion occurs in DLBCL, which may be associated with lower PTEN.

Preventive effect of LCZ696 on hypoxic pulmonary hypertension in rats via regulating the PI3K/AKT signaling pathway.

Hypoxic pulmonary hypertension (HPH) is a devastating disease worldwide; however, effective therapeutic drugs are lacking. This study investigated the effects and underlying mechanisms of LCZ696 treatment on hypoxia-induced pulmonary hypertension. Male Sprague-Dawley (SD) rats were kept in a hypobaric chamber with an oxygen concentration of 5% for 4 weeks. Rats were treated with either LCZ696 (18 mg/kg, 36 mg/kg, and 72 mg/kg) or sildenafil. The mean pulmonary artery pressure (mPAP), right ventricle hypertrophy index (RVHI), and lung system index were measured. Hematoxylin-eosin (HE) staining, Masson staining, and immunofluorescence staining were used for histological analysis. Enzyme linked immunosorbent assay (ELISA) kits were used to determine the concentrations of inflammatory and hypoxia-related factors. Western blotting was used to examine the expression of apoptotic and PI3K/AKT signaling pathway proteins in rat lung tissue. Hypoxia increased mPAP, RVHI, and lung system index and induced pulmonary vascular remodeling, pulmonary arteriomyosis, and pulmonary artery fibrosis. LCZ696 treatment reduced the increase in mPAP, RVHI, and the lung system index and ameliorated the induced pathological changes. Hypoxia upregulated expression of NF-kB, TNF-α, IL-6, HIF-1α, and Vascular endothelial growth factor (VEGF), decreased the ratio of Bax/Bcl-2, and activated the PI3K/AKT signaling pathway in lung tissue, and these effects were partially reversed by treatment with LCZ696. These results demonstrated that LCZ696 can ameliorate hypoxia-induced HPH by suppressing apoptosis, inhibiting the inflammatory response, and inhibiting the PI3K/AKT signaling pathway. It provides a reference for clinical rational drug use and lays a foundation for the study of HPH therapeutic drugs.

The immune checkpoint expression in the tumor immune microenvironment of DLBCL: Clinicopathologic features and prognosis.

Background & aims: The immune checkpoint recently provides a new strategy for the immunotherapy of malignant tumors. However, the role in the immune microenvironment of DLBCL is not completely clear. Methods: We detected the expression of PD-1, LAG-3, TIM-3, and TIGIT on TILs and on tumor cells among 174 DLBCL patients by IHC. Results: In TILs, the positive rates of PD-1, LAG-3, TIM-3 and TIGIT were 79.3%, 78.8%, 62.7% and 69.5%, respectively.TIM-3 and TIGIT were expressed in 44.8% and 45.4% of tumor cells. The expression of TIM-3 in TILs was significantly correlated with the Ann-Arbor stage (P=0.039). There was a positive correlation Between PD-1 and LAG-3 or TIM-3 and TIGIT.In addition, LAG-3 expression in TILs was associated with inferior prognosis.Multivariate analysis showed that PS score and R-CHOP therapy were independent risk factors for OS and PFS in patients with DLBCL (P=0.000). Conclusions: The expression level of TIM-3 is closely related to the Ann-Arbor stage, which may be expected to be a new index to evaluate the invasiveness of DLBCL. PD-1 was correlated with the expression of LAG-3, and the high expression of LAG-3 and LAG-3/PD-1 predicted the poor prognosis of DLBCL. Therefore, LAG-3 may become a new target of immunotherapy, or be used in combination with PD-1 inhibitors to improve the drug resistance of current patients with DLBCL.

Plasma Manganese Levels and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study.

Manganese (Mn) intake has been found to be linked with risk of type 2 diabetes. However, the role of Mn in the development of gestational diabetes mellitus (GDM) remains to be investigated. This prospective study included pregnant women from the Tongji Maternal and Child Health Cohort. A total of 2327 participants with plasma specimens before 20 weeks were included. Among the pregnant women, 9.7% (225/2327) were diagnosed with GDM. After adjustment, pregnant women with the third and highest quartile of plasma Mn levels had 1.31-fold (RR, 2.31 [1.48, 3.61]) and 2.35-fold (RR, 3.35 [2.17, 5.17]) increased risk of GDM compared with those with the lowest quartile. A 1 standard deviation increment of ln-transformed plasma Mn levels (0.53 µg/L) was related to elevated risks of GDM with RRs of 1.28 [1.17, 1.40]. The positive associations between Mn and GDM remained consistent in all the subgroups. The weighted quantile sum index was significantly related to GDM (RR, 1.60 [1.37, 1.86]). The contribution of Mn (58.69%) to the metal mixture index was the highest related to GDM. Higher plasma Mn levels were found to be linked with elevated fasting and 2 h post-load blood glucose. This study revealed relationships of higher plasma Mn levels in early pregnancy and increased risk of GDM, suggesting that though essential, excess Mn in the body might be a potential important risk factor for GDM.

Screening and identification of differentially expressed microRNAs in diffuse large B-cell lymphoma based on microRNA microarray.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell non-Hodgkin lymphoma in adults and the pathogenesis of DLBCL is multifactorial and complex. Understanding the molecular mechanisms involved in DLBCL is important to identify new therapeutic targets. The present study aimed to screen and identify differentially expressed microRNAs (miRNAs/miRs) between diffuse large B-cell lymphoma (DLBCL) and control [lymph node reactive hyperplasia (LRH)] groups, and to investigate whether miRNAs associated with DLBCL could serve as potential therapeutic targets. In total, 5 DLBCL experimental samples and 5 control samples were obtained from fresh patient tissues. Firstly, the fresh samples were analyzed using miRNA microarray to identify differentially expressed miRNAs. Next, three databases (TargetScan, microRNA.org and PITA) were used to predict by intersection the potential target genes of the 204 differential miRNAs identified, and a Venn diagram of the results was performed. Subsequently, the target genes of differential miRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Finally, to validate the miRNA microarray data, reverse transcription-quantitative PCR (RT-qPCR) was performed for 8 differentially expressed miRNAs (miR-193a-3p, miR-19a-3p, miR-19b-3p, miR-370-3p, miR-1275, miR-490-5p, miR-630 and miR-665) using DLBCL and LRH fresh samples. In total, 204 miRNAs exhibited differential expression, including 105 downregulated and 54 upregulated miRNAs. The cut-off criteria were set as P≤0.05 and fold-change ≥2. A total of 7,522 potential target genes for the 204 miRNAs were predicted. Potential target genes were enriched in the following pathways: 'Cancer', 'MAPK signaling pathway', 'regulation of actin cytoskeleton', 'focal adhesion', 'endocytosis', 'Wnt signaling pathway', 'axon guidance', 'calcium signaling pathway' and 'PI3K/AKT signaling pathway'. A total of 8 miRNAs were validated by RT-qPCR, and 4 miRNAs (miR-19b-3p, miR-193a-3p, miR-370-3p and miR-490-5p) exhibited low expression levels in DLBCL (P<0.05), while miR-630 was highly expressed in DLBCL (P<0.05). Overall, the present study screened 204 differentially expressed miRNAs and analyzed the expression levels of 8 differentially expressed miRNAs in DLBCL. These differentially expressed miRNAs may serve as therapeutic targets for improvement of therapeutic efficacy in DLBCL in the future.

Association between maternal plasma ferritin concentration, iron supplement use, and the risk of gestational diabetes: a prospective cohort study.

BACKGROUND: The association between iron supplementation and gestational diabetes mellitus (GDM) is still inconclusive, and this association has not been extensively studied in relation to plasma ferritin in the early second trimester. OBJECTIVES: We aimed to prospectively examine the independent and combined associations of plasma ferritin concentrations and iron supplement use with GDM. METHODS: We studied 2117 women from the Tongji Maternal and Child Health Cohort in Wuhan, China. Plasma ferritin around 16 weeks' gestation was measured by ELISA kits and information on iron supplement use was collected by questionnaires. GDM was diagnosed by a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks' gestation. A log-Poisson regression model was used to estimate the RR of GDM associated with plasma ferritin and iron supplementation. RESULTS: The median and IQR of plasma ferritin was 52.1 (29.6-89.9) ng/mL, and 863 (40.8%) participants reported use of iron supplements during the second trimester. A total of 219 (10.3%) participants developed GDM. Adjusted RRs (95% CIs) for GDM across increasing quartiles of plasma ferritin were 1.00 (reference), 2.14 (1.37, 3.34), 2.03 (1.30, 3.19), and 2.72 (1.76, 4.21), respectively. After adjustment, supplemental iron ≥60 mg/d during the second trimester was associated with an increased risk of GDM compared with nonusers (RR: 1.37; 95% CI: 1.02, 1.84). CONCLUSIONS: Both elevated plasma ferritin concentrations in the early second trimester and use of ≥60 mg/d of supplemental iron during pregnancy are independently associated with increased risk of GDM. Further clinical trials with precision nutrition approaches considering both baseline iron status and supplement use are needed to evaluate the benefits and risks of iron supplementation during pregnancy.

Association between Chinese Dietary Guidelines Compliance Index for Pregnant Women and Risks of Pregnancy Complications in the Tongji Maternal and Child Health Cohort.

BACKGROUND: Compliance with dietary guidelines among pregnant women can positively influence not only their own health but also the health of their babies. Measuring the compliance requires professional skills in nutrition and dietary counseling. In China, few simple and effective techniques assess dietary quality among pregnant women, especially in rural areas. We aimed to establish a new simple and effective assessment technique, the "Chinese Dietary Guidelines Compliance Index for Pregnant Women (CDGCI-PW)" and assess the association between maternal dietary compliance and risks of pregnancy complications. METHODS: The CDGCI-PW consists of 13 main components which were based on the 2016 edition of the Chinese dietary guidelines for pregnant women. Each component was assigned a different score range, and the overall score ranged from 0 to 100 points. The Tongji Maternal and Child Health Cohort study (from September 2013 to May 2016) was a prospective cohort study designed to examine maternal dietary and lifestyle effects on the health of pregnant women and their offspring. The maternal diet during the second trimester was compared with the corresponding recommended intake of the Chinese balanced dietary pagoda for pregnant women to verify their compliance with dietary guidelines. The association between maternal dietary quality and risks of pregnancy complications was estimated by regression analysis. Receiver operating characteristic (ROC) curves were constructed to identify the optimal cut-off values of CDGCI-PW for gestational hypertension and gestational diabetes mellitus (GDM). RESULTS: Among the 2708 pregnant women, 1489 were eventually followed up. The mean CDGCI-PW score was 74.1 (standard deviation (SD) 7.5) in the second trimester. The majority of foods showed the following trend: the higher the CDGCI-PW score, the higher the proportion of pregnant women who reported food intake within the recommended range. Moreover, a higher maternal CDGCI-PW score was significantly associated with lower risks of gestational hypertension [odds ratio (OR) (95% confidence interval [(CI): 0.30 (0.20, 0.37)] and GDM [OR (95% CI): 0.38 (0.31, 0.48)]. The optimal CDGCI-PW cut-off value for gestational hypertension was ≥68.5 (sensitivity 82%; specificity: 61%; area under the ROC curve, AUC = 0.743), and the optimal CDGCI-PW cut-off score for GDM was ≥75.5 (sensitivity 43%; specificity: 81%; area under the ROC curve, AUC = 0.714). CONCLUSIONS: The CDGCI-PW is a simple and useful technique that assesses maternal diet quality during pregnancy, while adherence to the CDGCI-PW is associated with a lower risk of gestational hypertension and GDM.

Association between dietary inflammatory index and gestational diabetes mellitus risk in a prospective birth cohort study.

OBJECTIVE: Information is limited regarding the possible relationship between diet-related inflammation and the risk of gestational diabetes mellitus (GDM). This study investigated the association between the inflammatory potential of the diet, measured by the dietary inflammatory index (DII), and GDM risk in pregnant Chinese women. METHODS: This study included 2639 eligible women from the Tongji Maternal and Child Health Cohort. Dietary intake was assessed by a validated semiquantitative food frequency questionnaire and was used to calculate the DII score. The DII was then validated using C-reactive protein measurements in a subsample of 133 pregnant women. GDM diagnoses were collected from medical records based on the results of a 75 g oral glucose tolerance test at 24 to 28 wk gestation. Multivariable-adjusted logistic regression models were performed to estimate the odds ratios (ORs) for GDM risk by DII score, modeled continuously and in tertiles. RESULTS: Of the 2639 participants, 13.1% were diagnosed with GDM. DII scores ranged from -4.45 to 3.15 and were positively associated with C-reactive protein (adjusted ß : 1.28, 95% confidence interval [CI]: 0.16, 2.40; P trend = 0.023) when comparing DII tertile 3 (most pro-inflammatory) to tertile 1 (most anti-inflammatory). A significant and positive association was observed between DII scores and GDM risk (adjusted OR: 1.43; 95% CI: 1.05, 1.95; P trend = 0.022) comparing the highest versus lowest tertiles. The stratified analysis showed that this association was stronger in pregnant women who were overweight or obese before pregnancy (adjusted OR: 2.20; 95% CI: 1.03, 4.69). CONCLUSIONS: These findings suggest that a higher DII score, corresponding to a more proinflammatory diet, is associated with a higher risk of GDM, particularly in pregnant women who were overweight or obese before pregnancy.

Effects of synthetic nitrogen fertilizer and manure on fungal and bacterial contributions to N2O production along a soil acidity gradient.

Reactive nitrogen (Nr) input often induces soil acidification, which may in turn affect bacterial and fungal nitrogen (N) transformations in soil and nitrous oxide (N2O) emissions. However, the interactive effects of soil acidity and Nr on the contributions of bacteria and fungi to N2O emissions remain unclear. We conducted a field experiment to assess the effects of anthropogenic Nr forms (i.e., synthetic N fertilizer and manure) on bacterial and fungal N2O emissions along a soil acidity gradient (soil pH = 6.8, 6.1, 5.2, and 4.2). The abundances and structure of bacterial and fungal communities were analyzed by real-time polymerase chain reaction and high-throughput sequencing techniques, respectively. Soil acidification reduced bacterial but increased fungal contributions to N2O production, corresponding respectively to changes in bacterial and fungal abundance. It also altered bacterial and fungal community structures and soil chemical properties, such as dissolved organic carbon and ammonia concentrations. Structural equation modeling (SEM) analyses showed that the soil properties and fungal community were the most important factors determining bacterial and fungal contributions to N2O emissions, respectively. The fertilizer form markedly affected N2O emissions from bacteria but not from fungi. Compared with synthetic N fertilizer, manure significantly lowered the bacterial contribution to N2O emissions in the soils with pH of 5.2 and 4.2. The manure application significantly increased soil pH but reduced nitrate concentration. The fertilizer form did not significantly alter the bacterial and fungal community structures. The SEM revealed that the fertilizer form affected the bacterial contribution to N2O production by changing the soil chemical properties. Together, these results indicated that soil acidification enhanced fungal dominance for N2O emission, and manure application has limited effects on fungal N2O emission, highlighting the challenges for mitigation of soil N2O emissions under future acid deposition and N enrichment scenarios.

Bidirectional Angle-Tolerant Polarization-Tuned Filtering and Wide-Range Refractive Index Sensing Based on Metal Film Coated Nanograting.

The miniaturization and integration of photonic devices are new requirements in the fast-growing optics field. In this paper, we focus on a feature-rich sub-wavelength nanograting-coated single-layer metal film. The numerical results show that the reflection behaviors of this proposed structure can realize bidirectional dual-channel ultra-narrowband polarized filtering and bidirectional wavelength-modulated sensing in a wide refractive index (RI) range from 1.0 to 1.4 for incident angle of 10° with transverse-magnetic (TM) polarized illumination at wavelengths between 550 nm to 1500 nm. Moreover, the bidirectional properties of filtering and sensing are not obviously decreased when increasing incident angle from 10° to 30°, and decreasing incident angle from 10° to 0°. The calculated RI sensitivity can be up to 592 nm/RIU with a high figure of merit (FOM) of 179.4 RIU-1. More to the point, this nanograting has a simple structure and is less sensitive to the height and shape of grating ridge, which provides great convenience for the fabrication of devices. The other thing that is going on is that this structure can also realize synchronously tunable color filtering, including green to red, with high color purity in the visible band by choosing the period. The underlying physical mechanism is analyzed in detail, and is primarily attributed to surface plasmon polariton (SPP) resonance and dipole resonance at double plasmon resonance wavelengths. This work has tremendous potential in developing multipurpose and high-performance integrated optical devices such as spectral filters, colored displays and plasmon biomedical sensors.

Proteomics reveals protein phosphatase 1γ as a biomarker associated with Hippo signal pathway in glioma.

Hub proteins related with Hippo signal pathway in glioma were investigated using proteomics methods (Tandem Mass Tag, TMT) to determine the differentially expressed proteins in glioblastoma (GBM). Ingenuity Pathway Analysis (IPA) was performed to complement proteomic findings by identifying the top canonical pathways as well as to suggest novel proteins for the targeted therapy of glioma. A total of 222 formalin-fixed paraffin-embedded (FFPE) glioma tissue samples were used to verify the expression of protein phosphatase 1γ (PP1γ), Yes-associated protein 1 (YAP1), and SOX2 via immunohistochemistry. Bioinformatics analysis revealed these proteins as crucial in the Hippo signaling pathway in GBM. Spearman correlation was performed to analyze the relationship of these three proteins, and survival analysis was conducted to investigate their effects on prognosis. Among the 5808 proteins identified by TMT with the standard of P-value < 0.05 and fold change (FC) of>1.2 or <0.83, 1398 upregulated and 1060 downregulated differentially expressed proteins were found. IPA revealed that the Hippo signaling was activated in the top 10 canonical pathways, and PP1γ was activated in the Hippo signaling. Immunohistochemistry analysis indicated that PP1γ, YAP1, and SOX2 were highly and positively expressed in glioma. PP1γ expression was related to WHO grade (p = 0.003) and ki-67 expression (p = 0.012). Low PP1γ expression was associated with IDH1-mut in low-grade glioma (LGG; WHO grades II and III) (p = 0.037). PP1γ was positively correlated with YAP1 (p < 0.001; r = 0.259) and SOX2 (p = 0.009; r = 0.175). In survival analysis, age, WHO grade, ki-67 expression, and PP1γ expression independently predicted a short OS in total cohort (p < 0.05). Therefore, PP1γ is a hub protein associated with Hippo signal pathway in glioma, and its expression indicates poor prognosis in patients with glioma. Therefore, PP1γ may be a promising prognostic biomarker and a therapeutic target in glioma.