Bacterial histone HBb from Bdellovibrio bacteriovorus compacts DNA by bending.

Histones are essential for genome compaction and transcription regulation in eukaryotes, where they assemble into octamers to form the nucleosome core. In contrast, archaeal histones assemble into dimers that form hypernucleosomes upon DNA binding. Although histone homologs have been identified in bacteria recently, their DNA-binding characteristics remain largely unexplored. Our study reveals that the bacterial histone HBb (Bd0055) is indispensable for the survival of Bdellovibrio bacteriovorus, suggesting critical roles in DNA organization and gene regulation. By determining crystal structures of free and DNA-bound HBb, we unveil its distinctive dimeric assembly, diverging from those of eukaryotic and archaeal histones, while also elucidating how it binds and bends DNA through interaction interfaces reminiscent of eukaryotic and archaeal histones. Building on this, by employing various biophysical and biochemical approaches, we further substantiated the ability of HBb to bind and compact DNA by bending in a sequence-independent manner. Finally, using DNA affinity purification and sequencing, we reveal that HBb binds along the entire genomic DNA of B. bacteriovorus without sequence specificity. These distinct DNA-binding properties of bacterial histones, showcasing remarkable similarities yet significant differences from their archaeal and eukaryotic counterparts, highlight the diverse roles histones play in DNA organization across all domains of life.

Histones, traditionally known for organizing and regulating DNA in eukaryotes and archaea, have recently been discovered in bacteria, opening up a new frontier in our understanding of genome organization across the domains of life. Our study investigates the largely unexplored DNA-binding properties of bacterial histones, focusing on HBb in Bdellovibrio bacteriovorus. We reveal that HBb is essential for bacterial survival and exhibits DNA-binding properties similar to archaeal and eukaryotic histones. However, unlike eukaryotic and archaeal histones, which wrap DNA, HBb bends DNA without sequence specificity. This work not only broadens our understanding of DNA organization across different life forms but also suggests that bacterial histones may have diverse roles in genome organization.

Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study.

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.

Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.

The 50% and 95% effective dose of remimazolam tosilate for anaesthesia induction in sleep disorders patients undergoing laparoscopic cholecystectomy: an up-and-down sequential allocation trial.

PURPOSE: Previous reports argue that preoperative sleep conditions of patients can influence the dosage of general anaesthesia drugs. Therefore, we aimed to investigate the dose-effect relationship of preoperative sleep disorders on the induction of general anaesthesia with remimazolam tosilate and calculate the Median effective (ED50) and 95% effective (ED95) dosages. METHODS: Included in our study were 56 patients who underwent laparoscopic cholecystectomy at our hospital. A separate group of 27 patients with sleep disorders (SD group) and 29 patients without sleep disorders (NSD group) using the Pittsburgh Sleep Quality Index (PSQI) were also included. According to the Dixon 'up-and-down' design, patients received remimazolam at preselected concentrations starting at 0.2 mg/kg. After the administration of remimazolam, loss of consciousness was observed. By observing whether consciousness disappeared within a minute, we adjusted the dose of remimazolam by 0.1 mg/kg (up and down) in the following patient. The Median effective dose (ED50), 95% effective dose (ED95), and 95% confidence interval (CI) of remimazolam for effective sedation were calculated. RESULTS: The ED50 of remimazolam was 0.226 mg/kg (95%CI 0.221-0.232 mg/kg) in the SD group and 0.191 mg/kg (95%CI, 0.183-0.199 mg/kg) in the NSD group. The ED95 of remimazolam was 0.237 mg/kg (95%CI 0.231-0.262 mg/kg) in the SD group and 0.209 mg/kg (95%CI 0.200-0.254 mg/kg) in the NSD group. CONCLUSIONS: In the SD group, the ED50 and ED95 of remimazolam during anaesthesia induction were 0.226 and 0.237 mg/kg, respectively. The induction dose of remimazolam in the SD group was significantly higher than that in the NSD group.

Analysis of pollutant dispersion patterns in rivers under different rainfall based on an integrated water-land model.

In the context of rapid urban expansion, the interaction between humanity and nature has become more prominent. Urban land and rivers often exist as distinct entities with limited material exchange. However, during rainfall, these two systems interconnect, resulting in the transfer of land-derived pollutants into rivers. Such transfer significantly increases river pollutant levels, adversely affecting water quality. Therefore, developing a water quality simulation and prediction model is crucial. This model should effectively illustrate pollutant movement and dispersion during rain events. This study proposes a comprehensive model that merges the Storm Water Management Model (SWMM) with the Environmental Fluid Dynamics Code (EFDC). This integrated model assesses the spread and dispersion of pollutants, including Ammonia Nitrogen (NH3-N), Total Phosphorus (TP), Total Nitrogen (TN), and Chemical Oxygen Demand (COD), within urban water cycles for various rainfall conditions, thus offering critical theoretical support for managing the water environment. The application of this model under different rainfall intensities (light, moderate and heavy) provides vital insights. During light rainfall, the river's natural purification process can sustain surface water quality at Class IV. Moderate rainfall causes accumulation of pollutants, reducing water quality to Class V. Conversely, heavy rainfall rapidly increases pollutant concentrations due to higher inflow, pushing the river to a degraded Class V status, which is beyond its natural purification capacity, necessitating engineering solutions to reattain Class IV quality. Furthermore, pollutant accumulation in downstream river sections is more influenced by flow rate than by rainfall intensity. In summary, the SWMM-EFDC integrated model proves highly effective in predicting river water quality, thereby significantly aiding urban water pollution control.

Computationally efficient composite triple beat cancellation for DML-based DA-RoF fronthaul.

The digital-analog radio-over-fiber (DA-RoF) scheme offers a high-fidelity and spectrally efficient solution for future mobile fronthaul. However, to be implemented in the low-cost directly modulated laser with direct detection (DML-DD) link, both the digital and analog parts in DA-RoF modulation would suffer from the composite second-order (CSO) and composite triple beat (CTB) caused by the chirp-dispersion interaction. In this Letter, we propose and experimentally demonstrate a computationally efficient composite triple beat cancellation (CTB-C) algorithm for DA-RoF fronthaul in the dispersion-uncompensated C-band DML-DD link. The CSO and CTB are suppressed at the receiver-side DSP based on the theoretical model of these nonlinear distortions. In the proof-of-concept experiment, a 1.2-dB improvement in the recovered signal-to-noise ratio (SNR) is obtained with 5.5-GHz 1024-QAM orthogonal frequency division multiplexing (OFDM) signal after 10-km standard single-mode fiber (SSMF) transmission. The proposed CTB-C technique does not require the training process and performs close to the Volterra-based feed-forward equalizer (VFE) under the complexity constraint.

ERK inhibition reduces neuronal death and ameliorates inflammatory responses in forebrain-specific Ppp2cα knockout mice.

It has been shown that PP2A is critical for apoptosis in neural progenitor cells. However, it remains unknown whether PP2A is required for neuronal survival. To address this question, we generated forebrain-specific Ppp2cα knockout (KO) mice. We show that Ppp2cα KO mice display robust neuronal apoptosis and inflammatory responses in the postnatal cortex. Previous evidence has revealed that PD98059 is a potent ERK inhibitor and may protect the brain against cell death after cardiac arrest. To study whether PD98059 may have any effects on Ppp2cα KO mice, the latter was treated with this inhibitor. We demonstrated that the total number of cleaved caspase3 positive (+) cells in the cortex was significantly reduced in Ppp2cα KO mice treated with PD98059 compared with those without PD98059 treatment. We observed that the total number of IBA1+ cells in the cortex was significantly decreased in Ppp2cα KO mice treated with PD98059. Mechanistic analysis reveals that deletion of PP2Aca causes DNA damage, which may be attenuated by PD98059. Together, this study suggests that inhibition of ERK may be an effective strategy to reduce cell death in brain diseases with abnormal neuronal apoptosis.

Unusual Increasing Viscoelasticity of Wormlike Micelles Composed of Imidazolium Gemini Surfactants with Temperature.

The viscoelasticity of wormlike micelles composed of ionic surfactants typically shows an exponential decrease with increasing temperature, which limits their application in relatively high-temperature (>90.0 °C) oilfields and the synthesis of functional materials as supramolecular templates at high temperatures. In this work, a series of imidazolium gemini surfactants, 1,9-(ethane-1,2-diyl)bis(3-alkyl-1H-imidazol-3-ium) bromide ([Cn-2-Cnim]Br2, n = 12, 14, 16, 18, 20), were synthesized. Their surface activities and aggregation behaviors in water were studied by electrical conductivity, rheology, polarization optical microscopy, small-angle X-ray scattering, ζ potential, and hydrogen nuclear magnetic resonance measurements. [C12-2-C12im]Br2 and [C14-2-C14im]Br2 mainly precipitate in water. [Cn-2-Cnim]Br2 (n = 16, 18, 20) forms lamellar liquid crystals over a large range of concentrations at low temperatures. With the increase of temperature, the lamellar liquid crystals transit to wormlike micelles. Interestingly, the viscoelasticity of the three wormlike micelles first increases to the maximum and then decreases with increasing temperature. These wormlike micelles without additives retain high viscoelasticity up to 90.0 °C or above. With the increase of the alkyl chain length of the surfactants, the transition temperature of lamellar liquid crystal to wormlike micelles and the disintegration temperature of wormlike micelles increase. The unusual increase of the viscoelasticity of wormlike micelles was due to the desorption of weakly bound counterions and the extension of the long hydrophobic chains of surfactants at high temperatures.

Fused diethynylbenzenes and phenanthrenes via arynes with alkynylsilanes.

A method for the hydroalkynylation and catalytic cyclization reactions of hexadehydro-Diels-Alder-derived benzynes is described. Diethynylbenzene derivatives are generated in a one-step reaction via trimethylsilyl-alkyne groups with benzyne formed by heating the appropriate tetrayne substrate. Trimethyl(phenylethynyl)silane loses TMS and binds to the electron-deficient site on HDDA-derived benzynes, and then phenanthrene was synthesized under mild reaction conditions by transition-metal-free, base promoted intramolecular cyclization.

[Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase â ¡b clinical trial].

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

Akt Regulates Sox10 Expression to Control Oligodendrocyte Differentiation via Phosphorylating FoxO1.

Sox10 is a well known factor to control oligodendrocyte (OL) differentiation, and its expression is regulated by Olig2. As an important protein kinase, Akt has been implicated in diseases with white matter abnormalities. To study whether and how Akt may regulate OL development, we generated OL lineage cell-specific Akt1/Akt2/Akt3 triple conditional knock-out (Akt cTKO) mice. Both male and female mice were used. These mutants exhibit a complete loss of mature OLs and unchanged apoptotic cell death in the CNS. We show that the deletion of Akt three isoforms causes downregulation of Sox10 and decreased levels of phosphorylated FoxO1 in the brain. In vitro analysis reveals that the expression of FoxO1 with mutations on phosphorylation sites for Akt significantly represses the Sox10 promoter activity, suggesting that phosphorylation of FoxO1 by Akt is important for Sox10 expression. We further demonstrate that mutant FoxO1 without Akt phosphorylation epitopes is enriched in the Sox10 promoter. Together, this study identifies a novel FoxO1 phosphorylation-dependent mechanism for Sox10 expression and OL differentiation.SIGNIFICANCE STATEMENT Dysfunction of Akt is associated with white matter diseases including the agenesis of the corpus callosum. However, it remains unknown whether Akt plays an important role in oligodendrocyte differentiation. To address this question, we generated oligodendrocyte lineage cell-specific Akt1/Akt2/Akt3 triple-conditional knock-out mice. Akt mutants exhibit deficient white matter development, loss of mature oligodendrocytes, absence of myelination, and unchanged apoptotic cell death in the CNS. We demonstrate that deletion of Akt three isoforms leads to downregulation of Sox10, and that phosphorylation of FoxO1 by Akt is critical for Sox10 expression. Together, these findings reveal a novel mechanism to regulate Sox10 expression. This study may provide insights into molecular mechanisms for neurodevelopmental diseases caused by dysfunction of protein kinases.

Pen-2 Negatively Regulates the Differentiation of Oligodendrocyte Precursor Cells into Astrocytes in the Central Nervous System.

Mutations on γ-secretase subunits are associated with neurologic diseases. Whereas the role of γ-secretase in neurogenesis has been intensively studied, little is known about its role in astrogliogenesis. Recent evidence has demonstrated that astrocytes can be generated from oligodendrocyte precursor cells (OPCs). However, it is not well understood what mechanism may control OPCs to differentiate into astrocytes. To address the above questions, we generated two independent lines of oligodendrocyte lineage-specific presenilin enhancer 2 (Pen-2) conditional KO mice. Both male and female mice were used. Here we demonstrate that conditional inactivation of Pen-2 mediated by Olig1-Cre or NG2-CreERT2 causes enhanced generation of astrocytes. Lineage-tracing experiments indicate that abnormally generated astrocytes are derived from Cre-expressing OPCs in the CNS in Pen-2 conditional KO mice. Mechanistic analysis reveals that deletion of Pen-2 inhibits the Notch signaling to upregulate signal transducer and activator of transcription 3, which triggers activation of GFAP to promote astrocyte differentiation. Together, these novel findings indicate that Pen-2 regulates the specification of astrocytes from OPCs through the signal transducer and activator of transcription 3 signaling.SIGNIFICANCE STATEMENT Astrocytes and oligodendrocyte (OLs) play critical roles in the brain. Recent evidence has demonstrated that astrocytes can be generated from OL precursor cells (OPCs). However, it remains poorly understood what mechanism governs the differentiation of OPCs into astrocytes. In this study, we took advantage of OL lineage cells specific presenilin enhancer 2 (Pen-2) conditional KO mice. We show that deletion of Pen-2 leads to dramatically enhanced astrocyte differentiation from OPCs in the CNS. Mechanistic analysis reveals that deletion of Pen-2 inhibits Hes1 and activates signal transducer and activator of transcription 3 to trigger GFAP activation which promotes astrocyte differentiation. Overall, this study identifies a novel function of Pen-2 in astrogliogenesis from OPCs.

Brij 30 Induced Transition of Rodlike Micelles to Wormlike Micelles and Gels in the Imidazole Ionic Liquid Surfactants: The Alkyl Chain Length Effect.

The effect of the hydrocarbon chain length of ionic liquid surfactants 1-hexadecyl-3-alkyl imidazolium bromide [C16imCn]Br (n = 1-16) on their aggregation behavior with polyoxyethylene lauryl ether (Brij 30) in aqueous solution was inspected. The rheological behavior, thermal properties, and microstructures of the different samples were studied using freeze-fractured electron microscopy. The interactions between [C16imCn]Br and Brij 30 were studied using nuclear magnetic resonance spectroscopy and theoretical simulation. With the addition of Brij 30, the rodlike micelles of [C16imCn]Br (n = 1, 2, 4, and 6) transition into wormlike micelles. The effects of the molar ratio of Brij 30 and [C16imCn]Br and the hydrocarbon chain length of [C16imCn]Br on the Brij 30/[C16imCn]Br (n = 1, 2, 4, and 6) wormlike micelles were studied. When Brij 30 was mixed with the rodlike micelles of [C16imC8]Br, the Brij 30/[C16imC8]Br mixtures form wormlike micelles at low Brij 30 concentration and gels at high Brij 30 concentration. The [C16imCn]Br (n = 10, 12, 14, and 16) rodlike micelles were induced by Brij 30 to turn into the Brij 30/[C16imCn]Br gels. The effect of the [C16imCn]Br hydrocarbon chain length on their rodlike micelles with the addition of Brij 30 is also theoretically discussed.

Bladder cancer diagnosis with a four-miRNA panel in serum.

Background: Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. Materials & methods: A total of 224 participants were involved in this three-cohort trial. A total of 15 candidate miRNAs were selected, and miRNAs with diagnostic ability were screened out with quantitative reverse transcription PCR. Diagnostic capability was ascertained by the receiver operating characteristic curve and area under the curve. Bioinformatics analysis was constructed for target gene prediction and functional annotation. Results: Six candidate miRNAs showed significantly different expression between bladder cancer patients and normal controls, and the final diagnostic panel comprised miR-181b-5p, miR-183-5p, miR-199-5p and miR-221-3p. Conclusion: This four-miRNA panel could represent a stable biomarker for bladder cancer diagnosis.

Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. After an experiment composed of 224 participants, the authors screened out six candidate miRNAs that may contribute to diagnosing bladder cancer. The authors also repeatedly verified the reliability of candidate miRNAs. Finally, a combination of multiple miRNAs, consisting of miR-181b-5p, miR-183-5p, miR-199-5p, and miR-221-3p, was better and more reliable in predicting bladder cancer occurrence.

[High-flow nasal cannula oxygen therapy in prostate-targeted needle biopsy in high-risk patients with obstructive sleep apnea syndrome].

OBJECTIVE: To compare the effect of high-flow nasal cannula oxygen therapy (HFNC) from that of conventional nasal cannula oxygen therapy (CNC) on oxygenation during prostate-targeted needle biopsy under total intravenous anesthesia in high-risk patients with obstructive sleep apnea syndrome (OSAS). METHODS: We randomly assigned 64 high-risk OSAS patients to two groups of an equal number to receive HFNC and CNC, respectively, under total intravenous anesthesia. We recorded the incidence rates of SpO2<95% and the lowest SpO2 during surgery, the mean arterial pressure (MAP), heart rate (HR) and oxygen saturation (SpO2) upon entering the operation room (T0), at the beginning (T1) and the end of surgery (T2) and at 30 minutes postoperatively (T3), as well as arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) at T0 and T2, and the incidence rates of airway intervention and adverse events, followed by comparison of the parameters between the two groups. RESULTS: Both the lowest SpO2 and PaO2 were significantly increased in the HFNC group compared with those in the CNC group (P < 0.05) while no statistically significant difference was observed in PaCO2 between the two groups (P > 0.05). The intraoperative incidence rates of hypoxia, airway intervention, choking and body movement were remarkably lower in the HFNC than in the CNC group (P < 0.05), but there were no statistically significant differences in the operation time, anesthesia duration and propofol dosage between the two groups (P > 0.05). CONCLUSION: HFNC may provide more adequate oxygenation, improve airway management, and reduce the incidence of hypoxemia in high-risk OSAS patients during prostate biopsy under total intravenous anesthesia.

Deletion of PDK1 in oligodendrocyte lineage cells causes white matter abnormality and myelination defect in the central nervous system.

PDK1 (3-Phosphoinositide dependent protein kinase-1) is a member in the PI3K (phosphatidylinositol 3 kinase) pathway and is implicated in neurodevelopmental disease with microcephaly. Although the role of PDK1 in neurogenesis has been broadly studied, it remains unknown how PDK1 may regulate oligogenesis in the central nervous system (CNS). To address this question, we generated oligodendrocyte (OL) lineage cells specific PDK1 conditional knockout (cKO) mice. We find that PDK1 cKOs display abnormal white matter (WM), massive loss of mature OLs and severe defect in myelination in the CNS. In contrast, these mutants exhibit normal neuronal development and unchanged apoptosis in the CNS. We demonstrate that deletion of PDK1 severely impairs OL differentiation. We show that genetic or pharmacological inhibition of PDK1 causes deficit in the mammalian target of rapamycin (mTor) signaling and down-regulation of Sox10. Together, these results highlight a critical role of PDK1 in OL differentiation during postnatal CNS development.

Lubrication and Dynamically Controlled Drug Release Properties of Tween 85/Tween 80/H2O Lamellar Liquid Crystals.

Lamellar liquid crystals have amazing lubricating and drug-solubilizing properties. Hence, the combination of drug molecules with lamellar liquid crystals is expected to be used in joint lubrication and treatment. In this study, the partial phase diagram of the Tween 85/Tween 80/H2O three-component system was determined. The phase structure of the system changed from a hexagonal liquid crystal to a lamellar liquid crystal with the increase of Tween 85 content. The lamellar liquid crystals showed superior lubricating properties due to their unique lamellar structure. Furthermore, the model of drug release during friction was established for the first time. It was found that the order of the lamellar liquid crystals increased with the increase of the mass ratio of Tween 85/Tween 80, leading to the decrease of the ibuprofen release rate. In addition, the release rate of ibuprofen increased progressively with the increase of the friction frequency, but the load had little effect on it. Therefore, the lamellar liquid crystals consisting of nonionic surfactants with good biocompatibility have potential application prospects for joint lubrication and treatment of arthritis.

Intramolecular N-Me and N-H aminoetherification for the synthesis of N-unprotected 3-amino-O-heterocycles.

A mild Rh-catalyzed method for synthesis of cyclic unprotected N-Me and N-H 2,3-aminoethers using an olefin aziridination-aziridine ring-opening domino reaction has been developed. The method is readily applicable to the stereocontrolled synthesis of a variety of 2,3-disubstituted aminoether O-heterocyclic scaffolds, including tetrahydrofurans, tetrahydropyrans and chromanes.

Loss of PP2A Disrupts the Retention of Radial Glial Progenitors in the Telencephalic Niche to Impair the Generation for Late-Born Neurons During Cortical Development†.

Telencephalic radial glial progenitors (RGPs) are retained in the ventricular zone (VZ), the niche for neural stem cells during cortical development. However, the underlying mechanism is not well understood. To study whether protein phosphatase 2A (PP2A) may regulate the above process, we generate Ppp2cα conditional knockout (cKO) mice, in which PP2A catalytic subunit α (PP2Acα) is inactivated in neural progenitor cells in the dorsal telencephalon. We show that RGPs are ectopically distributed in cortical areas outside of the VZ in Ppp2cα cKO embryos. Whereas deletion of PP2Acα does not affect the proliferation of RGPs, it significantly impairs the generation of late-born neurons. We find complete loss of apical adherens junctions (AJs) in the ventricular membrane in Ppp2cα cKO cortices. We observe abundant colocalization for N-cadherin and PP2Acα in control AJs. Moreover, in vitro analysis reveals direct interactions of N-cadherin to PP2Acα and to ß-catenin. Overall, this study not only uncovers a novel function of PP2Acα in retaining RGPs into the VZ but also demonstrates the impact of PP2A-dependent retention of RGPs on the generation for late-born neurons.

Semantic image segmentation of brain MRI with deep learning. / åŸºäºŽæ·±åº¦å­¦ä¹ çš„è„‘éƒ¨MRI解剖结构的语义分割.

OBJECTIVES: Previous studies on brain MRI image segmentation, such as threshold method, boundary detection method, and region method did not achieve good performance in complex scenes. Based on the deep learning segmentation technology, this study constructed a neural network model by using the algorithm of atrous convolution combined with conditional random field (CRF) to segment the thalamus, caudate nucleus, and lenticular nucleus in brain MRI, which laid a good foundation for MRI diagnosis of brain diseases. METHODS: A total of 1 200 MRI-Flair images of the brain were randomly selected, and 3 anatomical structures of thalamus, caudate nucleus, and lenticular nucleus were manually labeled, of which 1 000 were used as training data sets and 200 were used as test data sets. The neural network model was established by using deep convolutional neural networks (DCNN) combined with CRF algorithm. The training data set was input into the model, and the parameterized neural network model was obtained after iteration for 30 000 times. The test data set was used to evaluate, test, and output the predicted image. RESULTS: The model optimization results showed that the new brain MRI segmentation model DeepXAG had the highest accuracy. Therefore, DeepXAG was selected as the segmentation algorithm. The mean intersection over union (mIOU) of the DeepXAG model was 72.3%, which was significantly higher than other classical segmentation algorithms (CRF-RNN1, FCN-8s2, DPN3, RefineNet4, and PSPNet5). CONCLUSIONS: The DeepXAG algorithm has good accuracy and robustness in segmenting the anatomical structure of brain MRI images.

Conditional Inactivation of Pen-2 in the Developing Neocortex Leads to Rapid Switch of Apical Progenitors to Basal Progenitors.

The transition of apical progenitors (APs) to basal progenitors (BPs) is an important neurogenic process during cortical expansion. Presenilin enhancer 2 (Pen-2, also named as Psenen) is a key subunit of γ-secretase and has been implicated in neurodevelopmental disease. However, it remains unknown how Pen-2 may regulate the maintenance of APs. To address this question, we generated a conditional KO (cKO) mouse in which Pen-2 is specifically inactivated in neural progenitor cells in the telencephalon. Both male and female embryos were used. We show that Pen-2 cKO cortices display remarkable depletion of Aps, but transient increase on BPs, compared with controls. We demonstrate that the proliferation rate of APs or BPs is not changed, but the switch of APs to BPs is dramatically accelerated in Pen-2 cKO cortices. Molecular analyses reveal decreased levels of Hes1 and Hes5 but increased levels of Ngn2 and NeuroD1 in Pen-2 KO cells. We report that expression of Notch1 intracellular domain in Pen-2 cKO cortices restores the population of APs and BPs. In summary, these findings highlight a central role of the Notch signaling in Pen-2-dependent maintenance of neural stem cells in the developing neocortex.SIGNIFICANCE STATEMENT Presenilin enhancer 2 (Pen-2) has been implicated in neurodevelopmental disease. However, mechanisms by which Pen-2 regulates cortical development are not understood. In this study, we generated neural progenitor cell-specific Pen-2 conditional KO mice. We observe depletion of apical progenitors and transiently increased the number of basal progenitors in the developing neocortex of Pen-2 mutant mice. Mechanistic analyses reveal decreased levels of Hes1 and Hes5, but increased levels of neurogenic transcription factors in Pen-2 mutant cortices, compared with controls. We demonstrate that reintroduction of Notch intracellular domain into mutant mice restores the population of apical progenitors to basal progenitors. The above findings strongly suggest that the Pen-2-Notch pathway plays an essential role in the maintenance of neural stem cells during cortical development.