Ornithine δ-aminotransferase OsOAT is critical for male fertility and cold tolerance during rice plant development.

Cold stress is a major factor limiting the production and geographical distribution of rice (Oryza sativa) varieties. However, the molecular mechanisms underlying cold tolerance remain to be elucidated. Here, we report that ornithine δ-aminotransferase (OsOAT) contributes to cold tolerance during the vegetative and reproductive development of rice. osoat mutant was identified as a temperature-sensitive male sterile mutant with deformed floral organs and seedlings sensitive to cold stress. Comparative transcriptome analysis showed that OsOAT mutation and cold treatment of the wild-type plant led to similar changes in the global gene expression profiles in anthers. OsOAT genes in indica rice Huanghuazhan (HHZ) and japonica rice Wuyungeng (WYG) are different in gene structure and response to cold. OsOAT is cold-inducible in WYG but cold-irresponsive in HHZ. Further studies showed that indica varieties carry both WYG-type and HHZ-type OsOAT, whereas japonica varieties mostly carry WYG-type OsOAT. Cultivars carrying HHZ-type OsOAT are mainly distributed in low-latitude regions, whereas varieties carrying WYG-type OsOAT are distributed in both low- and high-latitude regions. Moreover, indica varieties carrying WYG-type OsOAT generally have higher seed-setting rates than those carrying HHZ-type OsOAT under cold stress at reproductive stage, highlighting the favorable selection for WYG-type OsOAT during domestication and breeding to cope with low temperatures.

Ectopic Colonization and Immune Landscapes of Periodontitis Microbiota in Germ-Free Mice With Streptozotocin-Induced Type 1 Diabetes Mellitus.

A two-way relationship between diabetes and periodontitis has been discussed recently. Periodontitis microbiota might affect the immune homeostasis of diabetes, but the molecular mechanism of their interactions is still not clear. The aims of this study were to clarify the possible immune regulatory effects of periodontitis microbiota on diabetes and the correlation between immunomodulation and ectopic colonization. A model of germ-free mice with streptozotocin-induced type 1 diabetes mellitus (T1D), which was orally inoculated with mixed saliva samples for 2 weeks, was used in this study. Those mice were randomly divided into two groups, namely, SP (where the T1D mice were orally inoculated with mixed saliva samples from periodontitis patients) and SH (where the T1D mice were orally inoculated with mixed saliva samples from healthy subjects). Ectopic colonization of saliva microbiota was assessed using culture-dependent method and Sanger sequencing, and the composition of gut microbiota was analyzed using 16S rRNA gene sequencing. Changes in 15 types of immune cells and six cytokines either from the small intestine or spleen were detected by multicolor flow cytometry. The correlation between gut microbiota and immune cells was evaluated by redundancy analysis. Although periodontitis microbiota minorly colonized the lungs, spleens, and blood system, they predominantly colonized the gut, which was mainly invaded by Klebsiella. SH and SP differed in beta diversity of the gut bacterial community. Compared to SH, microbial alteration in small intestine occurred with an increase of Lacticaseibacillus, Bacillus, Agathobacter, Bacteroides, and a decrease of Raoultella in SP. More types of immune cells were disordered in the spleen than in the small intestine by periodontitis microbiota, mainly with a dramatical increase in the proportion of macrophages, plasmacytoid dendritic cells (pDCs), monocytes, group 3 innate lymphoid cells, CD4-CD8- T cells and Th17 cells, as well as a decline of αßT cells in SP. Cytokines of IFNγ, IL17, and IL22 produced by CD4 + T cells as well as IL22 produced by ILCs of small intestine rose in numbers, and the intestinal and splenic pDCs were positively regulated by gut bacterial community in SP. In conclusion, periodontitis microbiota invasion leads to ectopic colonization of the extra-oral sites and immune cells infiltration, which might cause local or systemic inflammation. Those cells are considered to act as a "bridge" between T1D and periodontitis.

Immune Responses Regulated by Key Periodontal Bacteria in Germ-Free Mice.

The immune dysregulation induced by periodontal bacteria has important roles in the development of periodontitis. However, the role of key periodontal bacteria in local and systemic immunity has not been comprehensively studied. Herein, to explore immunoregulation maps of key periodontal bacteria, a mono-colonized germ-free mice model with P. gingivalis, F. nucleatum, and T. denticola for two weeks was designed in this study. The alveolar bone loss was determined by micro-CT. A total of 14 types of innate and adaptive immune cells of the gingiva, spleen, and colon were detected by multi-color flow cytometry. P. gingivalis induced the strongest innate immune response in gingiva and mononuclear phagocytes (MNPs) changed most significantly, compared to F. nucleatum and T. denticola. Immune dysregulation of the colon was widely induced by F. nucleatum. T. denticola mainly induced immune disorder in spleen. ILC3s, Tregs, CD11B+ dendritic cells s, MNPs, macrophages, and plasmacytoid dendritic cells were the main types in response to key periodontal bacteria. However, the alveolar bone loss was not induced by key periodontal bacteria. In conclusion, the overall immunoregulation of monomicrobial stimuli to decipher the complexities of periodontitis was provided in this study. P. gingivalis, F. nucleatum, and T. denticola have different effects on local and systemic immunity in gingiva, colon, and spleen of germ-free mice.

Channel Contribution In Deep Learning Based Automatic Sleep Scoring - How Many Channels Do We Need?

Machine learning based sleep scoring methods aim to automate the process of annotating polysomnograms with sleep stages. Although sleep signals of multiple modalities and channels should contain more information according to sleep guidelines, most multi-channel multi-modal models in the literature showed only a little performance improvement compared to single-channel EEG models and sometimes even failed to outperform them. In this paper, we investigate whether the high performance of single-channel EEG models can be attributed to specific model features in their deep learning architectures and to which extent multi-channel multi-modal models take the information from different channels of modalities into account. First, we transfer the model features from single-channel EEG models, such as combinations of small and large filters in CNNs, to multi-channel multi-modal models and measure their impacts. Second, we employ two explainability methods, the layer-wise relevance propagation as post-hoc and the embedded channel attention network as intrinsic interpretability methods, to measure the contribution of different channels on predictive performance. We find that i) single-channel model features can improve the performance of multi-channel multi-modal models and ii) multi-channel multi-modal models focus on one important channel per modality and use the remaining channels to complement the information of the focused channels. Our results suggest that more advanced methods for aggregating channel information using complementary information from other channels may improve sleep scoring performance for multi-channel multi-modal models.

STQS: Interpretable multi-modal Spatial-Temporal-seQuential model for automatic Sleep scoring.

Sleep scoring is an important step for the detection of sleep disorders and usually performed by visual analysis. Since manual sleep scoring is time consuming, machine-learning based approaches have been proposed. Though efficient, these algorithms are black-box in nature and difficult to interpret by clinicians. In this paper, we propose a deep learning architecture for multi-modal sleep scoring, investigate the model's decision making process, and compare the model's reasoning with the annotation guidelines in the AASM manual. Our architecture, called STQS, uses convolutional neural networks (CNN) to automatically extract spatio-temporal features from 3 modalities (EEG, EOG and EMG), a bidirectional long short-term memory (Bi-LSTM) to extract sequential information, and residual connections to combine spatio-temporal and sequential features. We evaluated our model on two large datasets, obtaining an accuracy of 85% and 77% and a macro F1 score of 79% and 73% on SHHS and an in-house dataset, respectively. We further quantify the contribution of various architectural components and conclude that adding LSTM layers improves performance over a spatio-temporal CNN, while adding residual connections does not. Our interpretability results show that the output of the model is well aligned with AASM guidelines, and therefore, the model's decisions correspond to domain knowledge. We also compare multi-modal models and single-channel models and suggest that future research should focus on improving multi-modal models.

Maintenance of neural stem cell positional identity by mixed-lineage leukemia 1.

Neural stem cells (NSCs) in the developing and postnatal brain have distinct positional identities that dictate the types of neurons they generate. Although morphogens initially establish NSC positional identity in the neural tube, it is unclear how such regional differences are maintained as the forebrain grows much larger and more anatomically complex. We found that the maintenance of NSC positional identity in the murine brain requires a mixed-lineage leukemia 1 (Mll1)-dependent epigenetic memory system. After establishment by sonic hedgehog, ventral NSC identity became independent of this morphogen. Even transient MLL1 inhibition caused a durable loss of ventral identity, resulting in the generation of neurons with the characteristics of dorsal NSCs in vivo. Thus, spatial information provided by morphogens can be transitioned to epigenetic mechanisms that maintain regionally distinct developmental programs in the forebrain.

Salivary mycobiome dysbiosis and its potential impact on bacteriome shifts and host immunity in oral lichen planus.

The biodiversity of the mycobiome, an important component of the oral microbial community, and the roles of fungal-bacterial and fungal-immune system interactions in the pathogenesis of oral lichen planus (OLP) remain largely uncharacterized. In this study, we sequenced the salivary mycobiome and bacteriome associated with OLP. First, we described the dysbiosis of the microbiome in OLP patients, which exhibits lower levels of fungi and higher levels of bacteria. Significantly higher abundances of the fungi Candida and Aspergillus in patients with reticular OLP and of Alternaria and Sclerotiniaceae_unidentified in patients with erosive OLP were observed compared to the healthy controls. Aspergillus was identified as an "OLP-associated" fungus because of its detection at a higher frequency than in the healthy controls. Second, the co-occurrence patterns of the salivary mycobiome-bacteriome demonstrated negative associations between specific fungal and bacterial taxa identified in the healthy controls, which diminished in the reticular OLP group and even became positive in the erosive OLP group. Moreover, the oral cavities of OLP patients were colonized by dysbiotic oral flora with lower ecological network complexity and decreased fungal-Firmicutes and increased fungal-Bacteroidetes sub-networks. Third, several keystone fungal genera (Bovista, Erysiphe, Psathyrella, etc.) demonstrated significant correlations with clinical scores and IL-17 levels. Thus, we established that fungal dysbiosis is associated with the aggravation of OLP. Fungal dysbiosis could alter the salivary bacteriome or may reflect a direct effect of host immunity, which participates in OLP pathogenesis.

[The Effect of Interference of NLRP3 with shRNA on AGEs-induced Inflammatory Response in Myocardial Cell].

OBJECTIVE: This study aims to explore the effect of silence of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome on advanced glycation end products (AGEs)-induced myocardial injury. METHODS: The myocardial injury model was indued by AGEs. NLRP3 was silenced by shRNA. H9c2 cells were divided into four groups: H9c2 (control group); AGEs group; AGEs+sh-Ctrl group; AGEs+sh-NLRP3 group. The latter two groups of cells will first shRNA control (sh-Ctrl) and shRNA-NLRP3 (sh-NLRP3) plasmids were transfected into H9c2 cells, the last 3 cells were then treated for 24 h with 100 mg/L AGEs, establishment of H9c2 damage model, control cells were treated with solvent for 24 h; Apoptosis was measured by Hoechst33258 staining. The levels of interleukin (IL)-6, IL-18 and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). The protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-3, Caspase-9, nuclear factor κB (NF-κB) P65 and p-P65 were tested by Western blot. The nuclear NF-κB P65 levels were detected by immunofluorescent staining. RESULTS: The expressions of NLRP3, ASC, Caspase-3 and Caspase-9 in AGEs group and AGEs+sh-Ctrl group was higher than control group ( P<0.05). Compared with AGEs group, the expressions of NLRP3, ASC, Caspase-3 and Caspase-9 in AGEs+sh-NLRP3 group was decreased ( P<0.05). Compared with control group, the apoptosis and the levels of IL-6, IL-18 and IL-1ß in AGEs group and AGEs+sh-Ctrl group were elevated ( P<0.05). The apoptosis and the levels of IL-6, IL-18 and IL-1ß in AGEs+sh-NLRP3 group were lower than those of AGEs group ( P<0.05). The phosphorylation of NF-κB P65 and nuclear NF-κB P65 in AGEs group and AGEs+sh-Ctrl group were higher than control group ( P<0.05). Compared with AGEs group, the phosphorylation of NF-κB P65 and nuclear NF-κB P65 in AGEs+sh-NLRP3 group were reduced ( P<0.05). Conlusion Silencing of NLRP3 inflammasome alleviates AGEs-induced apoptosis and inflammatory response in myocardial cell via inhibiting NF-κB P65 activation.

Association between epicardial adipose tissue and adverse outcomes in coronary heart disease patients with percutaneous coronary intervention.

We assessed the relationship between the volume of epicardial adipose tissue and long-term outcomes in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). The patients with CHD were followed for at least 2 years after PCI. The epicardial adipose tissue volume (EATV) was measured using multi-slice computed tomography. Cox regression analysis was used to examine the relationship between EATV and clinical outcome. In this study, 500 patients were enrolled and followed up for a median of 25.2 months. The incidence of adverse cardiovascular events was 12.4%. No significant differences were observed in age, sex, proportion of patients with hypertension or diabetes, smoking, drinking, total cholesterol, triglyceride, high-density lipoprotein, or unstable angina pectoris among different EATV quartiles (P>0.05). The EATV was associated with body mass index (P<0.0001), low-density lipoprotein level (P=0.039), high-sensitivity C-reactive protein level (P<0.001), uric acid level (P=0.004), adiponectin level (P<0.001), and left ventricular ejection fraction (P<0.001). Kaplan-Meier analysis indicated a significant difference in survival rate of patients in EATV quartile 1 versus 4 (P=0.019). After adjusting for confounding factors, EATV quartile 4 (>216.15 cm3) was still associated with adverse cardiovascular outcomes (HR = 1.98, 95% CI: 1.15-4.47, P=0.023) compared with quartile 1 (<101.58 cm3). Our data suggest that EATV is an independent predictor of long-term major adverse cardiovascular events in CHD patients after PCI. Therefore, assessment of EATV using multi-slice computed tomography may contribute to risk stratification in these patients.

The trehalose-6-phosphate synthase TPS5 negatively regulates ABA signaling in Arabidopsis thaliana.

KEY MESSAGE: The TPS5 negatively regulates ABA signaling by mediating ROS level and NR activity during seed germination and stomatal closure in Arabidopsis thaliana. Trehalose metabolism is important in plant growth and development and in abiotic stress response. Eleven TPS genes were identified in Arabidopsis, divided into Class I (TPS1-TPS4) and Class II (TPS5-TPS11). Although Class I has been shown to have TPS activity, the function of most members of Class II remains enigmatic. Here, we characterized the biological function of the trehalose-6-phosphate synthase TPS5 in ABA signaling in Arabidopsis. TPS5 expression was induced by ABA and abiotic stress, and expression in epidermal and guard cells was dramatically increased after ABA treatment. Loss-of-function analysis revealed that tps5 mutants (tps5-1 and tps5-cas9) are more sensitive to ABA during seed germination and ABA-mediated stomatal closure. Furthermore, the H2O2 level increased in the tps5-1 and tps5-cas9 mutants, which was consistent with the changes in the expression of RbohD and RbohF, key genes responsible for H2O2 production. Further, TPS5 knockout reduced the amounts of trehalose and other soluble carbohydrates as well as nitrate reductase (NR) activity. In vitro, trehalose and other soluble carbohydrates promoted NR activity, which was blocked by the tricarboxylic acid cycle inhibitor iodoacetic acid. Thus, this study identified that TPS5 functions as a negative regulator of ABA signaling and is involved in altering the trehalose content and NR activity.

Assessment of the oral health behavior, knowledge and status among dental and medical undergraduate students: a cross-sectional study.

BACKGROUND: It is widely accepted that oral health plays an important role in overall health. Both dental and medical students are expected to possess good oral health awareness and work together for public oral health promotion especially in developing countries like China. The aim of this study was to assess the oral health knowledge, behavior and status of dental and medical undergraduate students in the first (fresh) and third year (before specialized courses) study. METHODS: A self-administered structured questionnaire with 13 questions was designed based on oral health knowledge, behavior and status and a cross-sectional study was conducted among the 1st, 3rd year dental students (1DS, 3DS) and medical students (1MS, 3MS) of Sichuan University in Chengdu, China, in the period of September-December 2017. The data was analyzed by chi-square test using IBM SPSS Statistics v. 21.0. RESULTS: The oral health behavior, consciousness and status of the 1st, 3rd year medical and dental students were not optimistic. Dental freshmen were slightly superior to the medical ones in terms of the brushing methods and the awareness of oral disease-systemic disease relationship. The junior dental students showed highly significant improvement than their counterparts, mainly in the items about frequency of brushing teeth, brushing methods of vertical scrub or Bass technique (66.3%), usage of floss or mouth wash (49.7%), causes of caries, periodontal diseases and system diseases (56.9-83.4%). The rates mentioned above were 36.1, 15.8%, 26.7-43.6% among 3MS, respectively. In terms of oral health status, significant differences were only observed in junior students. The prevalence rates of bad breath, gum bleeding, and tooth discoloration among 3DS were obviously lower than those of 3MS. However, only a total of 17.2% junior students had a good oral health, including 23.8% dental students and 11.4% medical students. CONCLUSIONS: Our study provided a new understanding of oral health knowledge, behavior and status among dental and medical students, which may help to promote the reform of oral health education and establish a model for clinicians and dentists to work together for improving oral health.

The rs3850641 polymorphism of the TNFSF4 gene increases the risk of myocardial infarction in a Chinese Han population.

Tumor necrosis factor superfamily member 4 (TNFSF4), also known as Ox40 ligand (Ox40l), plays an important role in atherosclerosis development. Several studies reported the association between the rs3850641 polymorphism of the TNFSF4 gene and the risk of myocardial infarction (MI). However, the results are inconsistent. In order to explore the relationship between the rs3850641 polymorphism of the TNFSF4 gene and MI, we conducted a case-control study including 454 cases and 512 controls in a Chinese Han population. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The present study found that AA genotype (AA vs. GG: odds ratio (OR) & 95% confidence interval (CI), 2.00(1.04,3.86), P=0.039; AA vs. AG+GG: OR & 95% CI, 1.93(1.00,3.70), P=0.049) or A allele carriers (A vs. G: OR & 95% CI, 1.27(1.00,1.60), P=0.047) of the rs3850641 polymorphism of the TNFSF4 gene increased the risk of MI. In conclusion, this case-control study confirms that the rs3850641 polymorphism of the TNFSF4 gene increases the risk of MI.

G-Protein-Coupled Receptor Gpr17 Regulates Oligodendrocyte Differentiation in Response to Lysolecithin-Induced Demyelination.

Oligodendrocytes are the myelin-producing cells of the central nervous system (CNS). A variety of brain disorders from "classical" demyelinating diseases, such as multiple sclerosis, stroke, schizophrenia, depression, Down syndrome and autism, are shown myelination defects. Oligodendrocyte myelination is regulated by a complex interplay of intrinsic, epigenetic and extrinsic factors. Gpr17 (G protein-coupled receptor 17) is a G protein-coupled receptor, and has been identified to be a regulator for oligodendrocyte development. Here, we demonstrate that the absence of Gpr17 enhances remyelination in vivo with a toxin-induced model whereby focal demyelinated lesions are generated in spinal cord white matter of adult mice by localized injection of LPC(L-a-lysophosphatidylcholine). The increased expression of the activated form of Erk1/2 (phospho-Erk1/2) in lesion areas suggested the potential role of Erk1/2 activity on the Gpr17-dependent modulation of myelination. The absence of Gpr17 enhances remyelination is correlate with the activated Erk1/2 (phospho-Erk1/2).Being a membrane receptor, Gpr17 represents an ideal druggable target to be exploited for innovative regenerative approaches to acute and chronic CNS diseases.

High-dose atorvastatin reduces the risk of cardiovascular events in patients with percutaneous coronary intervention.

We systematically searched in PubMed, Web of Science, Embase and China National Knowledge Infrastructure from the inception to March 31, 2017, identified relevant trials about efficacy of high-does Atorvastatin for patients with percutaneous coronary intervention. Twelve studies with the number of 2801 patients were included in the meta-analysis. Compared with control group, high-does Atorvastatin significantly reduced the risk of myocardial infarction in patients with percutaneous coronary intervention (Relative risk =0.62, 95% confidence interval: 0.49-0.78), with low level of heterogeneity (I2=22.6%, P=0.228). Nine studies with 2248 patients reported the adverse cardiovascular events. A fixed-effect model was applied. Compared with control group, patients with high-does Atorvastatin taken, the risk of adverse cardiovascular events was degraded by 65% (Relative risk, RR=0.65, 95% confidence interval (CI): 0.50-0.84), which was confirmed by trial sequential analysis as the cumulative Z curve entered the futility area. The subgroup analyses found that decreased risks of myocardial infarction among trails (RR=0.64, 95%CI: 0.50-0.83, RR=0.55, 95%CI: 0.34-0.88). Egger and Begg's test found no publication bias (t=-1.670, P=0.129; Z=1.560, P=0.119). The use of high-dose Atorvastatin could reduce the risk of myocardial infraction and cardiovascular adverse events in patients with percutaneous coronary intervention. High-dose Atorvastatin was recommended as an adjunct to aid percutaneous coronary intervention.

RPS9M, a Mitochondrial Ribosomal Protein, Is Essential for Central Cell Maturation and Endosperm Development in Arabidopsis.

During double fertilization of angiosperms, the central cell of the female gametophyte fuses with a sperm cell to produce the endosperm, a storage tissue that nourishes the developing embryo within the seed. Although many genetic mutants defective in female gametophytic functions have been characterized, the molecular mechanisms controlling the specification and differentiation of the central cell are still not fully understood. Here, we report a mitochondrial ribosomal protein, RPS9M, is required for central cell maturation. RPS9M was highly expressed in the male and female gametophytes before and after double fertilization. The female gametophytes were defective in the rps9m mutant specifically concerning maturation of central cells. The morphological defects include unfused polar nuclei and smaller central vacuole in central cells. In addition, embryo initiation and early endosperm development were also severely affected in rps9m female gametophytes even after fertilized with wild type pollens. The RPS9M can interact with ANK6, an ankyrin-repeat protein in mitochondria previously reported to be required for fertilization. The expression pattern and mutant phenotype of RPS9M are similar to those of ANK6 as well, suggesting that RPS9M may work together with ANK6 in controlling female gametophyte development, possibly by regulating the expression of some mitochondrial proteins.

Intracoronary administration of tirofiban during percutaneous coronary intervention facilitates patients with acute coronary syndrome.

We assessed the efficacy and safety of tirofiban intracoronary versus intravenous administration during percutaneous coronary intervention for patients with acute coronary syndrome. The databases of PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang Database were retrieved. A total of 437 articles were found, according to inclusive and exclusive criteria, 13 of which were finally included. Compared with subjects with intravenous administration, those with intracoronary administration were more likely to reach thrombolysis in myocardial infarction trial grade 3 flow (relative risk = 1.17, 95% confidence interval: 1.11-1.22), improve left ventricular ejection fraction (Standardized mean difference = 0.65, 95% confidence interval: 0.20-1.11). Intracoronary administration resulted in a reduced risk of major adverse cardiovascular events at 30-day follow-up (relative risk = 0.47, 95% confidence interval: 0.34-0.65). However, incidence of bleeding complications was not statistically significant between two groups (relative risk = 0.76, 95% confidence interval: 0.55-1.04). Intracoronary administration of tirofiban can be more effective in increasing coronary blood flow and microvascular perfusion, more effective in improving postoperative myocardial reperfusion, more significantly in reducing the incidence of adverse cardiovascular events at 30-day's follow-up and improving the prognosis after percutaneous coronary intervention without increasing the risk of bleeding.

Maintenance of neural stem cell regional identity in culture.

Neural stem cells (NSCs) are distributed throughout the ventricular-subventricular zone (V-SVZ) in the adult mouse brain. NSCs located in spatially distinct regions of the V-SVZ generate different types of olfactory bulb (OB) neurons, and the regional expression of specific transcription factors correlates with these differences in NSC developmental potential. In a recent article, we show that Nkx2.1-expressing embryonic precursors give rise to NKX2.1+ NSCs located in the ventral V-SVZ of adult mice. Here we characterize a V-SVZ monolayer culture system that retains regional gene expression and neurogenic potential of NSCs from the dorsal and ventral V-SVZ. In particular, we find that Nkx2.1-lineage V-SVZ NSCs maintain Nkx2.1 expression through serial passage and can generate new neurons in vitro. Thus, V-SVZ NSCs retain key aspects of their in vivo regional identity in culture, providing new experimental opportunities for understanding how such developmental patterns are established and maintained during development.

Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation.

Constitutive activation of Wnt/ß-catenin inhibits oligodendrocyte myelination. Tcf7l2/Tcf4, a ß-catenin transcriptional partner, is required for oligodendrocyte differentiation. How Tcf7l2 modifies ß-catenin signalling and controls myelination remains elusive. Here we define a stage-specific Tcf7l2-regulated transcriptional circuitry in initiating and sustaining oligodendrocyte differentiation. Multistage genome occupancy analyses reveal that Tcf7l2 serially cooperates with distinct co-regulators to control oligodendrocyte lineage progression. At the differentiation onset, Tcf7l2 interacts with a transcriptional co-repressor Kaiso/Zbtb33 to block ß-catenin signalling. During oligodendrocyte maturation, Tcf7l2 recruits and cooperates with Sox10 to promote myelination. In that context, Tcf7l2 directly activates cholesterol biosynthesis genes and cholesterol supplementation partially rescues oligodendrocyte differentiation defects in Tcf712 mutants. Together, we identify stage-specific co-regulators Kaiso and Sox10 that sequentially interact with Tcf7l2 to coordinate the switch at the transitions of differentiation initiation and maturation during oligodendrocyte development, and point to a previously unrecognized role of Tcf7l2 in control of cholesterol biosynthesis for CNS myelinogenesis.

Renal mucinous tubular and spindle cell carcinoma: report of four cases and literature review.

Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an unusual renal tumor. It is important to increase the recognition of the clinicopathological features of MTSCC-K and improve its clinical and differential diagnosis. This report described four cases of MTSCC-K with clinical, imaging, and pathological examination and showed that the tumor boundaries of MTSCC-K were clear, and tumor cells arranged into tubules and cord-like beams, between which was lightly stained myxoid stroma. The tumor cells were smaller and cube- or oval-shaped, with single small eosinophilic nucleoli, low-grade nuclei, and little nuclear fission. The myxoid stroma was scattered around lymphocytes and plasma cells. Immunohistochemical markers including CK7, CD117, EMA (epithelial membrane antigen), vimentin, and CK8/18, showed positive expression in tumor cells, but the tumor cells were negative for CD10 and villin. The proliferation index of Ki-67 was 5-10%. Since MTSCC-K is a rare low-grade malignancy, with unique histological and immunohistochemical characteristics, it is important for clinicians and pathologists to have a defined awareness of this tumor type in order to decrease the rate of misdiagnosis.

Mixing regime as a key factor to determine DON formation in drinking water biological treatment.

Dissolved organic nitrogen (DON) can act as precursor of nitrogenous disinfection by-products formed during chlorination disinfection. The performances of biological fluidized bed (continuous stirred tank reactor, CSTR) and bio-ceramic filters (plug flow reactor, PFR) were compared in this study to investigate the influence of mixing regime on DON formation in drinking water treatment. In the shared influent, DON ranged from 0.71mgL(-1) to 1.20mgL(-1). The two biological fluidized bed reactors, named BFB1 (mechanical stirring) and BFB2 (air agitation), contained 0.12 and 0.19mgL(-1) DON in their effluents, respectively. Meanwhile, the bio-ceramic reactors, labeled as BCF1 (no aeration) and BCF2 (with aeration), had 1.02 and 0.81mgL(-1) DON in their effluents, respectively. Comparative results showed that the CSTR mixing regime significantly reduced DON formation. This particular reduction was further investigated in this study. The viable/total microbial biomass was determined with propidium monoazide quantitative polymerase chain reaction (PMA-qPCR) and qPCR, respectively. The results of the investigation demonstrated that the microbes in BFB2 had higher viability than those in BCF2. The viable bacteria decreased more sharply than the total bacteria along the media depth in BCF2, and DON in BCF2 accumulated in the deeper media. These phenomena suggested that mixing regime determined DON formation by influencing the distribution of viable, total biomass, and ratio of viable biomass to total biomass.