ADAMTS4 Enhances Oligodendrocyte Differentiation and Remyelination by Cleaving NG2 Proteoglycan and Attenuating PDGFRα Signaling.

Although NG2 is known to be selectively expressed in oligodendrocyte precursor cells (OPCs) for many years, its expressional regulation and functional involvement in oligodendrocyte differentiation have remained elusive. Here, we report that the surface-bound NG2 proteoglycan can physically bind to PDGF-AA and enhances PDGF receptor alpha (PDGFRα) activation of downstream signaling. During differentiation stage, NG2 protein is cleaved by A disintegrin and metalloproteinase with thrombospondin motifs type 4 (Adamts4), which is highly upregulated in differentiating OPCs but gradually downregulated in mature myelinating oligodendrocytes. Genetic ablation of Adamts4 gene impedes NG2 proteolysis, leading to elevated PDGFRα signaling but impaired oligodendrocyte differentiation and axonal myelination in both sexes of mice. Moreover, Adamts4 deficiency also lessens myelin repair in adult brain tissue following Lysophosphatidylcholine-induced demyelination. Thus, Adamts4 could be a potential therapeutic target for enhancing oligodendrocyte differentiation and axonal remyelination in demyelinating diseases.SIGNIFICANCE STATEMENT NG2 is selectively expressed in OPCs and downregulated during differentiation stage. To date, the molecular mechanism underlying the progressive removal of NG2 surface proteoglycan in differentiating OPCs has been unknown. In this study, we demonstrate that ADAMTS4 released by differentiating OPCs cleaves surface NG2 proteoglycan, attenuates PDGFRα signaling, and accelerates oligodendrocyte differentiation. In addition, our study also suggests ADAMTS4 as a potential therapeutic target for promoting myelin recovery in demyelinating diseases.

Predict the prevalence and incidence of Parkinson's disease using fractal interpolation-LSTM model.

The investigation of the prediction of disease population is a noticeable exploration topic in the field of sciences. As a type of neurological disease, the incidence and prevalence of Parkinson's disease are still difficult to accurately study. In this paper, a method is proposed to forecast the number of incident cases (NumIn), incidence rate (InRa), the number of prevalent cases (NumPr), and prevalence rate (PrRa) of Parkinson's disease in ten countries selected. Using past data on the incidence rate, the number of prevalent cases, and the prevalence rate from 1990 to 2019, three types of fractal interpolations with different fractal dimensions are constructed for reconstructing the past data, where the vertical scaling factors are determined by the method proposed in this article. Then, the Long Short-Term Memory (LSTM) model is employed to forecast the values of NumIn, InRa, NumPr, and PrRa with Parkinson's disease in 2020. Meanwhile, the autoregressive integrated moving average model is used to predict the values compared with the LSTM model. The evaluation metrics employed for error calculation include the root mean square error and the coefficient of determination (R2). According to the proposed optimal criteria, the best predicted results are the average of three types of prediction values based on the LSTM model by analyzing and comparing eight predicted results.

Toxicity Study on Crude Alkaloid Extracts of Houttuyniae herba Based on Zebrafish and Mice.

Houttuyniae herba has a long history of medicinal and edible homology in China. It has the functions of clearing heat and detoxifying, reducing swelling and purulent discharge, diuresis, and relieving gonorrhea. It is mainly distributed in the central, southeastern, and southwestern provinces of China. Houttuyniae herba has been designated by the National Ministry of Health of China as a dual-use plant for both food and medicine. Comprising volatile oils, flavonoids, and alkaloids as its primary constituents, Houttuyniae herba harbors aristolactams, a prominent subclass of alkaloids. Notably, the structural affinity of aristolactams to aristolochic acids is discernible, the latter known for its explicit toxicological effects. Additionally, the safety study on Houttuyniae herba mainly focused on the ethanol, methanol, or aqueous extract. In this study, both zebrafish and mice were used to evaluate the acute toxicity of the total alkaloids extracts from Houttuyniae herba (HHTAE). The zebrafish experiment showed that a high concentration (0.1 mg/mL) of HHTAE had a lethal effect on zebrafish embryos. Furthermore, the mice experiment results showed that, even at a higher dose of 2000 mg/kg, HHTAE was not toxic. In conclusion, HHTAE was of low safety risk.

SECISBP2L-Mediated Selenoprotein Synthesis Is Essential for Autonomous Regulation of Oligodendrocyte Differentiation.

Thyroid hormone (TH) controls the timely differentiation of oligodendrocytes (OLs), and its deficiency can delay myelin development and cause mental retardation. Previous studies showed that the active TH T3 is converted from its prohormone T4 by the selenoprotein DIO2, whose mRNA is primarily expressed in astrocytes in the CNS. In the present study, we discovered that SECISBP2L is highly expressed in differentiating OLs and is required for DIO2 translation. Conditional knock-out (CKO) of Secisbp2l in OL lineage resulted in a decreased level of DIO2 and T3, accompanied by impaired OL differentiation, hypomyelination and motor deficits in both sexes of mice. Moreover, the defective differentiation of OLs in Secisbp2l mutants can be alleviated by T3 or its analog, but not the prohormone T4. The present study has provided strong evidence for the autonomous regulation of OL differentiation by its intrinsic T3 production mediated by the novel SECISBP2L-DIO2-T3 pathway during myelin development.SIGNIFICANCE STATEMENT Secisbp2l is specifically expressed in differentiating oligodendrocytes (OLs) and is essential for selenoprotein translation in OLs. Secisbp2l regulates Dio2 translation for active thyroid hormone (TH) T3 production in the CNS. Autonomous regulation of OLs differentiation via SECISBP2L-DIO2-T3 pathway.

Secondary Mycobacterium abscessus Infection after Debridement in Child with Dog Bite: a Case Report.

BACKGROUND: In recent years, there have been increasing reports related to infection caused by Mycobacterium abscessus (MAB). As one of the most common mycobacterium iatrogenic infections, it is characterized by pulmonary infection. However, only a few reports of MAB-related skin and soft tissue infections are available. This study reported a 3-year-old child admitted to our hospital for a dog bite with MAB infection after debridement. METHODS: The diagnosis of MAB in this child was made after detecting the bacteria in the wound secretion based on secretion culture in clinical laboratory. RESULTS: The result of the first bacterial isolation and culture of wound secretion was negative. However, the results were positive two days later and was diagnosed as MAB infection for samples of the purulent secretions collected by puncture and aspiration during debridement from the red and swollen regions of the thigh. The drug sensitivity results suggested that the child was sensitive to cefoxitin. However, she was resistant to amikacin, linezolid, minocycline, imipenem, tobramycin, moxifloxacin, clarithromycin, and doxycycline. The combined treatment strategy was used for managing MAB infection with a good effect. CONCLUSIONS: The management of MAB soft tissue infection has limitations, like poor tolerance, toxicity, and mul¬ti-drug interaction. The combined treatment strategy is important for MAB infection, and monitoring adverse re-actions and toxicity is the key.

A Combination of In Silico ADMET Prediction, In Vivo Toxicity Evaluation, and Potential Mechanism Exploration of Brucine and Brucine N-oxide-A Comparative Study.

Brucine (BRU) and brucine N-oxide (BNO) are prominent, bioactive, and toxic alkaloids in crude and processed Semen Strychni. Studies have demonstrated that BRU and BNO possess comprehensive pharmacological activities, such as anti-inflammatory and analgesic. In this context, a comparative study of BRU and BNO was performed by combination analysis of in silico ADMET prediction, in vivo toxicity evaluation, and potential action mechanism exploration. ADMET prediction showed that BRU and BNO might induce liver injury, and BRU may have a stronger hepatoxic effect. The prediction was experimentally verified using the zebrafish model. The BRU-induced hepatotoxicity of zebrafish larvae had a dose-response relationship. The mechanism of BRU-induced hepatotoxicity might relate to phosphorylation, kinase activity, and signal transduction. By comparison, signal transduction and gap junctions might involve BNO-induced hepatotoxicity. Our results provided a better understanding of BRU- and BNO-induced hepatotoxicity. We also built a foundation to elucidate the material base of the hepatotoxicity of traditional Chinese medicine Semen Strychni.

New Transition Metal Coordination Polymers Derived from 2-(3,5-Dicarboxyphenyl)-6-carboxybenzimidazole as Photocatalysts for Dye and Antibiotic Decomposition.

Coordination polymers (CPs) are an assorted class of coordination complexes that are gaining attention for the safe and sustainable removal of organic dyes from wastewater discharge by either adsorption or photocatalytic degradation. Herein, three different coordination polymers with compositions [Ni(HL)(H2O)2·1.9H2O] (1), [Mn3(HL)(L)(µ3-OH)(H2O)(phen)2·2H2O] (2), and [Cd(HL)4(H2O)]·H2O (3) (H3L = 2-(3,5-dicarboxyphenyl)-6-carboxybenzimidazole; phen = 1,10-phenanthroline) have been synthesized and characterized spectroscopically and by single crystal X-ray diffraction. Single crystal X-ray diffraction results indicated that 1 forms a 2D layer-like framework, while 2 exhibits a 3-connected net with the Schläfli symbol of (44.6), and 3 displays a 3D supramolecular network in which two adjacent 2D layers are held by π···π interactions. All three compounds have been used as photocatalysts to catalyze the photodegradation of antibiotic dinitrozole (DTZ) and rhodamine B (RhB). The photocatalytic results suggested that the Mn-based CP 2 exhibited better photodecomposition of DTZ (91.1%) and RhB (95.0%) than the other two CPs in the time span of 45 min. The observed photocatalytic mechanisms have been addressed using Hirshfeld surface analyses.

Transcriptome analysis of long non-coding RNAs reveals NR_015556 lncRNA is a novel regulator for adipocyte differentiation.

Long non-coding RNAs (lncRNAs) have gained extensive attentions due to their significant roles in diverse biological process. However, the potential functions of lncRNAs participation in adipocyte differentiation have not been fully explored. In the present study, we globally profiled lncRNA expression using lncRNA microarray and identified 1745 lncRNA probes with differential expression on day 0 and day 4 post-induction in both C3H10T1/2 mesenchymal stem cells and 3T3-L1 preadipocytes. Furthermore, we showed that stable shRNA knockdown (KD) of NR_015556, a novel lncRNA that was significantly down-regulated in adipocyte differentiation, promoted adipocyte differentiation by increasing the number of lipid droplets and adipocyte markers such as Fabp4, Adipsin and Fasn. Mechanistically, NR_015556 KD attenuated the expression of Wnt signaling components Wnt10b and non-phospho (active) ß-catenin, and elevated adipocyte master factors Ppar-γ and C/EBPα levels. Conversely, pharmacological activation of Wnt10b-ß-catenin signaling by LiCl suppressed NR_015556 KD-induced enhancement of adipocyte differentiation and Ppar-γ and C/EBPα expression levels. Taken together, these results indicate that down-regulation of NR_015556 promotes adipocyte differentiation through inhibiting Wnt10b-ß-catenin signaling pathway and then elevating Ppar-γ and C/EBPα triggered transcriptional cascades.

Risk factors for antibiotic resistance and mortality in patients with bloodstream infection of Escherichia coli.

This study aimed to investigate the risk factors for bloodstream infection (BSI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) and related mortality. The clinical data of 388 patients with E. coli BSI were analyzed. Blood cultures were performed and the antimicrobial susceptibility profiles of the resulting isolates were determined. Four single-nucleotide polymorphisms (rs231775, rs12343816, rs16944, and rs2233406) were genotyped using real-time PCR. ESBL were detected by disk diffusion confirmatory testing. Univariate and multivariate regression analyses were applied to identify the risk factors for ESBL-producing isolates and the BSI-induced mortality. The prevalence of ESBL-producing E. coli in BSI patients was 40.98%. E. coli isolates were commonly susceptible to carbapenem and ß-lactam/ß-lactamase inhibitor combinations. The major ESBL genes were CTX-M-14, CTX-M-55, CTX-M-15, and CTX-M-27. The proportion of CTX-M-15 was significantly higher in patients over 70 years and those receiving stomach tube catheterization. Nosocomial infection, biliary tract infection, stomach tube catheterization, and previous cephalosporin administration were independent risk factors for ESBL-producing isolates. ESBL positivity, nosocomial infection, and cancer were independent risk factors of mortality. Two genetic polymorphisms associated with inflammation activation, rs231775 A allele and rs2233406 T allele, significantly increased the mortality risk of E. coli BSI with a risk ratio (95% CI) of 1.93 (1.05-3.55) and 4.38 (2.07-9.29), respectively. For patients with nosocomial infection, biliary tract infection, and cancer, the monitor of BSI and antibiotic susceptibility should be enhanced. The invasive procedures should be minimized. rs231775 and rs2233406 are promising prognostic markers for E. coli BSI patients.

Hidden blood loss of minimally invasive hybrid lumbar interbody fusion: an analysis of influencing factors.

BACKGROUND: Lumbar interbody fusion(LIF) is the leading way to treat Lumbar Degenerative Diseases(LDD). At present, there is a lack of research on the influencing factors of hidden blood loss in minimally invasive hybrid lumbar interbody fusion. This study comprehensively explores the definite factors affecting the hidden blood loss in minimally invasive hybrid lumbar interbody fusion. MATERIALS AND METHODS: One hundred patients with Lumbar degenerative diseases who underwent minimally invasive hybrid lumbar interbody fusion in our center were included. Demographics, laboratory data, surgical data, and radiographic data were collected. The Gross equation and Sehat equation were used to calculate the estimated value of hidden blood loss. Multi-factor linear regression analysis was used to determine the influencing factors of hidden blood loss. RESULT: We reviewed and collected 100 patients who underwent minimally invasive hybrid approach, mean age 65 ± 10 years, male: female 37:63; 17 patients of diabetes and 83 patients of non-diabetes; Total blood loss was 645.59 ± 376.37 ml, hidden blood loss was 421.39 ± 337.45 ml, the hidden blood loss percentage was 57 ± 26%. Results from the multi-factorial linear regression model: Diabetes (p < 0.05), hypertension (p < 0.05), psoas thickness (p < 0.05) and dorsal extensor group thickness (p < 0.05) were potential risk factors for postoperative hidden blood loss. CONCLUSION: Although minimally invasive hybrid approach is minimally invasive surgery, there is still a significant amount of hidden blood loss. There is a greater risk of blood loss in diabetes, hypertension and preoperative MRI assessment of thickness of the psoas, thickness of the dorsal extensor group.

Comprehensive Evaluation of the Quality of Tripterygium Glycosides Tablets Based on Multi-Component Quantification Combined with an In Vitro Biological Assay.

Tripterygium glycosides tablets (TGTs) are widely used in clinical practice to treat rheumatoid arthritis and other autoimmune diseases, with significant beneficial effects but also high toxicity, necessitating rigorous quality evaluation and control. In current study, a rapid resolution liquid chromatography tandem electrospray ionization triple quadrupole mass spectrometry (RRLC-ESI-MS/MS) method was developed and validated for the quantitative analysis of 14 components of ten batches of TGTs produced by different manufacturers, including four diterpenoids, three triterpenoids, and seven sesquiterpene alkaloids. Meanwhile, the NO inhibition effects of these TGTs were evaluated in LPS-induced RAW264.7 cells for their downstream anti-inflammatory activities, as well as their cytotoxicity. The results indicate that the TGTs from different manufacturers showed poor quality consistency, as evidenced by large variations in chemical profiles and biological effects, which may increase the risks associated with clinical use. To improve the quality status of TGTs, it is crucial to identify indicator components whose characterization can accurately reflect the efficacy and toxicity of TGTs from which they were derived. Our study reveals that triptolide, triptoquinone B, celastrol, and demethylzelaysteral considerably contributed to the anti-inflammatory activity and/or cytotoxicity of TGTs, implying that they should be further investigated as candidate indicator components for TGT quality control.

Rapid Analysis of Aristolochic Acids and Aristolactams in Houttuyniae Herba by LC-MS/MS.

Houttuyniae herba, the Saururaceae plant Houttuynia cordata Thunb., has multiple therapeutic effects, including clearing heat, eliminating toxins, reducing swelling, discharging pus, and relieving stagnation. It has a long history as an edible and medicinal plant in China. Phytochemical studies show that the main constituents include volatile oil, flavonoids, and alkaloids. Aristolactam is a major alkaloid with a structure similar to toxic aristolochic acids. However, there has been no systematic study on aristolochic acids and alkaloids in Houttuyniae herba. Therefore, in this study, an LC-MS/MS method was developed to simultaneously detect seven alkaloids and five aristolochic acids in Houttuyniae herba from different origins. Six alkaloids (O-demethyl nornucifrine, N-nornucifrine, aristololactam AII, aristololactam FI, aristololactam BII, cepharadione B) were found and quantitatively determined in 75 batches of samples. Meanwhile, no aristolochic acids or aristololactams were found in Houttuyniae herba at a limit of detection (LOD) of ≤4 ng/mL. The method developed was fully validated in terms of LOD, limit of quantification (LOQ), linearity, precision, accuracy, and stability. These data clarify the content of the above safety-related components in Houttuyniae herba and provide a reference for further research into its safety.

Recent Advances of Silver-Based Coordination Polymers on Antibacterial Applications.

With the continuous evolution of bacteria and the constant use of traditional antibiotics, the emergence of drug-resistant bacteria and super viruses has attracted worldwide attention. Antimicrobial therapy has become the most popular and important research field at present. Coordination Polymer (CP) and/or metal-organic framework (MOF) platforms have the advantages of a high biocompatibility, biodegradability, and non-toxicity, have a great antibacterial potential and have been widely used in antibacterial treatment. This paper reviewed the mechanism and antibacterial effect of three typical MOFs (pure Ag-MOFs, hybrid Ag-MOFs, and Ag-containing-polymer @MOFs) in silver-based coordination polymers. At the same time, the existing shortcomings and future views are briefly discussed. The study on the antibacterial efficacy and mechanism of Ag-MOFs can provide a better basis for its clinical application and, meanwhile, open up a novel strategy for the preparation of more advanced Ag-contained materials with antibacterial characteristics.

[Spectral characteristics of sesquiterpene pyridine alkaloids from Tripterygium plants].

Sesquiterpene pyridine alkaloids are important components in Tripterygium plants, possessing a wide range of pharmacological activities, such as anti-inflammation immunosuppression, anti-tumor, anti-virus, and deinsectization, and are of great research value. They are composed of highly oxidized dihydro-ß-furansquiterpene and pyridine dicarboxylic acid through ester bonds. According to the structural characteristics of pyridine dicarboxylic acid fragments, they can be divided into various structural subtypes. Up to now, more than 110 sesquiterpene pyridine alkaloids have been isolated and identified from Tripterygium plants. This study reviewed the structural features and spectral(i.e., UV, IR, MS, and NMR) characteristics of sesquiterpene pyridine alkaloids and summarized the structural elucidation process in detail to provide references for their further research and development.

Trimetazidine offers myocardial protection in elderly coronary artery disease patients undergoing non-cardiac surgery: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Trimetazidine (TMZ) pretreatment protects cardiomyocytes during cardiac surgery. TMZ may protect elderly patients with ischaemic heart disease (IHD) undergoing non-cardiac surgery. METHODS: This was a randomized, double-blind, placebo-controlled trial (registration #ChiCTR1900025018) of patients with IHD scheduled to undergo non-cardiac surgery at Shenzhen People's Hospital (Shenzhen, Guangdong Province, China) between June 2014 and September 2015, randomized to 60 mg TMZ or placebo 12 h before surgery. The primary endpoint was the occurrence of in-hospital cardiovascular events. The secondary endpoints were myocardial ischaemia on five-lead electrocardiogram (cECG), cardiac troponin I (cTnI) elevation, cardiac death, acute coronary events, heart failure, and arrhythmia requiring treatments. RESULTS: Compared with the placebo group, the TMZ group showed a lower occurrence of in-hospital cardiovascular events (primary endpoint, 20.0% vs. 37.5%, P = 0.02), myocardial ischaemia (15.0% vs. 32.5%, P < 0.01), cTnI elevation (2.5% vs. 10%, P < 0.01), acute coronary events (10.0% vs. 20.0%, P < 0.05), heart failure (0% vs. 2.5%, P < 0.05), and arrhythmia requiring treatment (17.5% vs. 35.0%, P < 0.05). There was no acute myocardial infarction during the 30-day postoperative period. CONCLUSIONS: In elderly patients with IHD undergoing non-cardiac surgery, TMZ pretreatment was associated with myocardial protective effects. Trial registration The trial was prospectively registered at http://www.chictr.org.cn/showproj.aspx?proj=41909 with registration number [ChiCTR1900025018] (7/8/2019).

Reinforced macromolecular micelle-crosslinked hyaluronate gels induced by water/DMSO binary solvent.

Introducing macromolecular micelles into a biocompatible hyaluronic acid (HA) hydrogel is a promising strategy to improve its mechanical properties for biomedical applications. However, it is still unclear whether the solvent nature has an influence on the structure and property of HA gels especially when they are used for those cases containing binary solvents because reversible hydrophobic association within micelles could be weakened or even dissociated by organic solvents. In this work, we demonstrated that a binary solvent consisting of water and low-toxic dimethyl sulfoxide (DMSO), a commonly used cryoprotectant agent in biomedicine, can enhance the mechanical properties of hydrophobic-associated methacrylated hyaluronate (MeHA) gels crosslinked by diacrylated PEO99-PPO65-PEO99 (F127DA) macromolecular micelles, namely FH gels. The resulting FH hydro/organo-gels showed a crystalline structure due to polymer/solvent interactions. The FH gels showed a low swelling degree and the maximum strength (10.12 MPa), modulus (106.8 kPa) and toughness (1540 J m-2) in DMSO with a volume fraction of around 0.6. Moreover, the FH gels displayed a rapid recoverability under cyclic loading-unloading stress particularly in the presence of DMSO within the network due to their dual-dynamic dissipation networks. Such novel hydrophobic associated polysaccharide gels with tunable mechanical properties in binary solvents would be attractive in a cryopreservation system for cell-based applications.

Alleviative effects of dietary microbial floc on copper-induced inflammation, oxidative stress, intestinal apoptosis and barrier dysfunction in Rhynchocypris lagowski Dybowski.

The heavy metal poisoning in humans and fish represents a significant global problem. Copper (Cu), as an essential micronutrient in human and animal metabolism, often accumulates excessively in aquatic environment. The microbial floc is rich in a variety of probiotics and bioactive compounds, which has been documented to have the functions of antioxidant and immunoenhancement. A 64-day experiment was conducted to investigate the protective effects and potential mechanisms of dietary supplementation of microbial floc and Cu exposure on inflammatory response, oxidative stress, intestinal apoptosis and barrier dysfunction in Rhynchocypris lagowski Dybowski. A total of four hundred fifty R. lagowski were fed five experimental diets containing graded levels of microbial floc from 0% to 16% (referred to as B0, B4, B8, B12 and B16, respectively) in the first 60 days, and 96 h of acute copper exposure test was carried out in the last four days. The results showed that microbial floc exerted significant alleviative effects by preventing alterations in the levels of bioaccumulation, caspase3, caspase8, caspase9, malondialdehyde and interleukin-6, improving the activities of lysozyme, complement C3, complement C4, immunoglobulin M, alkaline phosphatase, heat shock protein 70, heat shock protein 90 and glutathione peroxidase, catalase, superoxide dismutase, total antioxidant capacity. In addition, microbial floc assisted in regulating the expression of NF-κB/Nrf2 signaling molecule genes, including NF-κB, TNF-α, IL-1ß, IL-8, IL-10, TGF-ß, Keap1, Nrf2, Maf, HO-1, CAT, CuZn-SOD, GCLC and GPX. Overall, our results suggest that dietary supplementation with of microbial floc can alleviate copper-induced inflammation, oxidative stress, intestinal apoptosis and barrier dysfunction in R. lagowski. A suitable supplementation level of approximately 12% microbial floc is recommended in the present study.

Multiple endo bronchial lipoma: a rare case report.

BACKGROUND: Endobronchial lipoma is an extremely rare benign tumor, which is generally located in the first three subdivisions of the tracheobronchial tree. According to the existing literature, all endobronchial lipomas are single (one per patient). Here, we report a rare case in which the patient presented with two endobronchial lipomas in the same patient, and underwent a bronchoscopic tumor resection in the left main bronchus and the left lower bronchus. Both tumors were pathologically confirmed as endobronchial lipoma. CASE PRESENTATION: A 52-year-old Chinese man presented at the clinic reporting a mild cough with yellow color sputum and exertional dyspnea for 2 weeks. He was a heavy smoker (45 pack-years). Chest auscultation demonstrated faint wheezing in left lower lobe. Computed tomography (CT) revealed two low-density endobronchial masses located in the middle segment of the left main bronchus and the posterior basilar segmental bronchus of the left lower lobe. The neoplasms measured a CT-attenuation value of -70HU, -98HU in density with air trapping and atelectasis in the segmental bronchus of the left lower lobe. The patient underwent interventional bronchoscopic management to remove the neoplasms by using an electrosurgical snare, cryotherapy, and electrocautery. The locations of the neoplasms were confirmed at the left main bronchus and the superior segment of the left lower lobe during bronchoscopic intervention. Histopathological examination confirmed that both tissues were consistent with lipomas. After 18 months of follow-up, the patient was free of symptoms and CT revealed that bronchiectasia remained in the superior segment of the left lower lobe; however, no mass lesion was present in the left bronchus. CONCLUSIONS: This case suggests that an endobronchial lipoma can present as multiple lesions, and both proximal and distal types can simultaneously occur in the same patient. Thus, these findings help us further understand the biology of endobronchial lipomas.

WNT signaling represses astrogliogenesis via Ngn2-dependent direct suppression of astrocyte gene expression.

Neural progenitor cells (NPCs) are sequentially specified into neurons and glia during the development of central nervous system. WNT/ß-catenin signaling is known to regulate the balance between the proliferation and differentiation of NPCs during neurogenesis. However, the function of WNT/ß-catenin signaling during gliogenesis remains poorly defined. Here, we report that activation of WNT/ß-catenin signaling disrupts astrogliogenesis in the developing spinal cord. Conversely, inhibition of WNT/ß-catenin signaling leads to precocious astrogliogenesis. Further analysis reveals that activation of WNT/ß-catenin pathway results in a dramatic increase of neurogenin 2 (Ngn2) expression in transgenic mice, and knockdown of Ngn2 expression in neural precursor cells can reverse the inhibitory effect of WNT/ß-catenin on astrocytic differentiation. Moreover, Ngn2 can directly bind to the promoters of several astrocyte specific genes and suppress their expression independent of STATs activity. Together, our studies provide the first in vivo evidence that WNT/ß-catenin signaling inhibits early astrogliogenesis via an Ngn2-dependent transcriptional repression mechanism.

Long non-coding RNA lnc-OAD is required for adipocyte differentiation in 3T3-L1 preadipocytes.

Long non-coding RNAs (lncRNAs) have gained extensive attentions due to their significant roles in diverse biological process. However, the potential functions of lncRNAs participation in adipocyte differentiation have not been fully explored. Here we identified a long non-coding RNA called lnc-OAD (lncRNA associated with osteoblast and adipocyte differentiation, transcribed from 1700018A04Rik gene), which modulated 3T3-L1 adipocyte differentiation. Lnc-OAD was up-regulated expression during 3T3-L1 differentiation and stable knockdown of lnc-OAD inhibited adipocyte differentiation in 3T3-L1 cells. Further mechanisms study revealed that silencing of lnc-OAD strongly elevated the protein expression of ß-catenin, and then decreased expression of adipocyte master transcription factors PPAR-γ and C/EBPα. The addition of IWR-1 up-regulated the expression of PPAR-γ and C/EBPα and rescued the impairment of adipocyte differentiation caused by lnc-OAD knockdown. Meanwhile, we also found mitotic clonal expansion (MCE) during the early stage of adipocyte differentiation was inhibited in lnc-OAD-knockdown cells. Taken together, our study reveals a novel function of lnc-OAD in modulating adipogenesis via influencing mitotic clonal expansion and regulating WNT/ß-catenin signaling pathway.