Patterned cPCDH expression regulates the fine organization of the neocortex.

The neocortex consists of a vast number of diverse neurons that form distinct layers and intricate circuits at the single-cell resolution to support complex brain functions1. Diverse cell-surface molecules are thought to be key for defining neuronal identity, and they mediate interneuronal interactions for structural and functional organization2-6. However, the precise mechanisms that control the fine neuronal organization of the neocortex remain largely unclear. Here, by integrating in-depth single-cell RNA-sequencing analysis, progenitor lineage labelling and mosaic functional analysis, we report that the diverse yet patterned expression of clustered protocadherins (cPCDHs)-the largest subgroup of the cadherin superfamily of cell-adhesion molecules7-regulates the precise spatial arrangement and synaptic connectivity of excitatory neurons in the mouse neocortex. The expression of cPcdh genes in individual neocortical excitatory neurons is diverse yet exhibits distinct composition patterns linked to their developmental origin and spatial positioning. A reduction in functional cPCDH expression causes a lateral clustering of clonally related excitatory neurons originating from the same neural progenitor and a significant increase in synaptic connectivity. By contrast, overexpression of a single cPCDH isoform leads to a lateral dispersion of clonally related excitatory neurons and a considerable decrease in synaptic connectivity. These results suggest that patterned cPCDH expression biases fine spatial and functional organization of individual neocortical excitatory neurons in the mammalian brain.

A Liquid Biopsy Signature for the Early Detection of Gastric Cancer in Patients.

BACKGROUND & AIMS: Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC. METHODS: The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using transcriptomic profiling in discovery phase. The extracellular vesicle (EV)-derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69). RESULTS: In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073-0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi'an cohort, AUC: 0.8839; 95% CI: 0.8336-0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597-0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other gastrointestinal tumor plasma samples indicated its GC specificity. CONCLUSIONS: EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.

Surgical evidence-based comparison of [68Ga]Ga-FAPI-04 PET and MRI-DWI for assisting debulking surgery in ovarian cancer patients.

PURPOSE: Imaging assessment of abdominopelvic tumor burden is crucial for debulking surgery decision in ovarian cancer patients. This study aims to compare the efficiency of [68Ga]Ga-FAPI-04 FAPI PET and MRI-DWI in the preoperative evaluation and its potential impact to debulking surgery decision. METHODS: Thirty-six patients with suspected/confirmed ovarian cancer were enrolled and underwent integrated [68Ga]Ga-FAPI-04 PET/MRI. Nineteen patients (15 stage III-IV and 4 I-II stage) who underwent debulking surgery were involved in the diagnostic efficiency analysis. The images of [68Ga]Ga-FAPI-04 PET and MRI-DWI were visually analyzed respectively. Immunohistochemistry on FAP was performed in metastatic lesions to investigate the radiological missing of [68Ga]Ga-FAPI-04 PET as well as its different performance in primary debulking surgery (PDS) and interval debulking surgery (IDS) patients. Potential imaging impact on management was also studied in 35 confirmed ovarian cancer patients. RESULTS: [68Ga]Ga-FAPI-04 PET displayed higher sensitivity (76.8% vs.59.9%), higher accuracy (84.9% vs. 80.7%), and lower missing rate (23.2% vs. 40.1%) than MRI-DWI in detecting abdominopelvic metastasis. The diagnostic superiority of [68Ga]Ga-FAPI-04 PET is more obvious in PDS patients but diminished in IDS patients. [68Ga]Ga-FAPI-04 PET outperformed MRI-DWI in 70.8% abdominopelvic regions (17/24), which contained seven key regions that impact the resectability and surgical complexity. MRI-DWI hold advantage in the peritoneal surface of the bladder and the central tendon of the diaphragm. Of the contradictory judgments between the two modalities (14.9%), [68Ga]Ga-FAPI-04 PET correctly identified more lesions, particularly in PDS patients (73.8%). In addition, FAP expression was independent of lesion size and decreased in IDS patients. [68Ga]Ga-FAPI-04 PET changed 42% of surgical planning that was previously based on MRI-DWI. CONCLUSION: [68Ga]Ga-FAPI-04 PET is more efficient in assisting debulking surgery in ovarian cancer patients than MRI-DWI. Integrated [68Ga]Ga-FAPI-04 PET/MR imaging is a potential method for planning debulking surgery in ovarian cancer patients.

LMNB1 deletion in ovarian cancer inhibits the proliferation and metastasis of tumor cells through PI3K/Akt pathway.

Ovarian cancer (OC) is a common malignant tumor in gynecology. LMNB1 is an important component of the nuclear skeleton. The expression of LMNB1 in ovarian cancer is significantly higher than that in normal tissues, but its role in tumor still needs comprehensive investigation. In this study, we overexpressed and knocked down LMNB1 in ovarian cancer cells and explore the effect of LMNB1 on the cell proliferation, migration and the underlying mechanism. We analyzed the expression levels of LMNB1 in ovarian cancer and their clinical relevance by using bioinformatics methods, qRT-PCR, Western blot and immunohistochemistry. To state the effect and mechanism of LMNB1 on OC in vitro and in vivo, we performed mouse xenograft studies, CCK8, cloning formation, Edu incorporation, wound healing, transwell and flow cytometry assay in stable LMNB1 knockdown OC cells, following by RNA-seq. Overexpression of LMNB1 indicates the progression of OC. LMNB1 knockdown inhibited the proliferation and migration of OC cells by suppressing the FGF1-mediated PI3K-Akt signaling pathway. Our study shows LMNB1 as a novel prognostic factor and therapeutic target in OC.

EIF5A2 Is Involved in the Biological Process of Cervical Cancer Cells through AGR2.

INTRODUCTION: Cervical cancer is a severe malignant tumor that endangers the health of women worldwide. Eukaryotic initiation factor-5A2 (EIF5A2) expression has been reported to be increased in cervical cancer and correlates with prognosis. An attempt was made in this paper to explore the impact and potential mechanisms of EIF5A2 in the cell biology of cervical cancer. METHODS: We first knocked down EIF5A2 in cervical cancer cells. Then, we examined the proliferation, migration, invasion, and apoptosis of these cells by cell counting kit 8, wound healing, Transwell, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Cells were processed with different concentrations of cisplatin to observe their sensitivity to cisplatin. Next, the relationship between EIF5A2 and anterior gradient 2 (AGR2) was verified by co-immunoprecipitation. Following AGR2 overexpression, the biological processes of these cells were examined. RESULTS: EIF5A2 knockdown inhibited cell proliferation, migration, and invasion, and it promoted apoptosis and enhanced the sensitivity to cisplatin in cervical cancer cells. Additionally, AGR2 expression was positively correlated with EIF5A2, and its overexpression alleviated the reduction in proliferation, migration, and invasion of cervical cancer cells induced by EIF5A2 knockdown. Overexpression of AGR2 also reduced apoptosis and their sensitivity to cisplatin in EIF5A2-knockdwon cervical cancer cells. CONCLUSION: EIF5A2 knockdown inhibited the biological process of cervical cancer cells through modulation of AGR2. The in-depth investigation of the molecular mechanism of EIF5A2 in cervical cancer cells provides new strategies for the prevention and treatment of clinical malignancies.

Modification methods and applications of egg protein gel properties: A review.

Egg protein (EP) has a variety of functional properties, such as gelling, foaming, and emulsifying. The gel characteristics provide a foundation for applications in the food industry and research on EP. The proteins denature and aggregate to form a dense three-dimensional gel network structure, with a process influenced by protein concentration, pH, ion type, and strength. In addition, the gelation properties of EP can be altered to varying degrees by applying different treatment conditions to EP. Currently, modification methods for proteins include physical modification (heat-induced denaturation, freeze-thaw modification, high-pressure modification, and ultrasonic modification), chemical modification (glycosylation modification, phosphorylation modification, acylation modification, ethanol modification, polyphenol modification), and biological modification (enzyme modification). Pidan, salted eggs, egg tofu, and other egg products have unique sensory properties, due to the gel properties of EP. In accessions, EP has also been used as a new ingredient in food packaging and biopharmaceuticals due to its gel properties. This review will further promote EP gel research and provide guidance for its full application in many fields.

Activation of PKM2 metabolically controls fulminant liver injury via restoration of pyruvate and reactivation of CDK1.

Accumulating evidence indicates that metabolic events profoundly modulate the progression of various diseases. Pyruvate is a central metabolic intermediate in glucose metabolism. In the present study, the metabolic status of pyruvate and its pharmacological significance has been investigated in mice with lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced fulminant liver injury. Our results indicated that LPS/D-Gal exposure decreased the activity of pyruvate kinase and the content of pyruvate, which were reversed by the PKM2 activator TEPP-46. Pretreatment with TEPP-46 or supplementation with the cell-permeable pyruvate derivate ethyl pyruvate (EP) attenuated LPS/D-Gal-induced liver damage. Interestingly, post-insult intervention of pyruvate metabolism also resulted in beneficial outcomes. The phospho-antibody microarray analysis and immunoblot analysis found that the inhibitory phosphorylation of cyclin dependent kinase 1 (CDK1) was reversed by TEPP-46, DASA-58 or EP. In addition, the therapeutic benefits of PKM2 activator or EP were blunted by the CDK1 inhibitor Ro 3306. Our data suggests that LPS/D-Gal exposure-induced decline of pyruvate might be a novel metabolic mechanism underlies the development of LPS/D-Gal-induced fulminant liver injury, PKM2 activator or pyruvate derivate might have potential value for the pharmacological intervention of fulminant liver injury.

Treatment of primary cardiac angiosarcoma in a 35 weeks pregnant woman.

BACKGROUND: Cardiac angiosarcoma is a rare but highly malignant cardiac tumor. It is characterized by poor prognosis, and current treatment approaches are not effective. CASE PRESENTATION: A 37-year-old female with 35 weeks pregnancy experienced chest tightness and shortness of breath for 1 month. She was diagnosed with primary cardiac angiosarcoma. Delivery of fetus was performed early to treat the mother. The patient underwent resection of the tumor then she was treated with chemotherapy. However, the tumor recurred 11 months after surgery. CONCLUSION: Angiosarcoma is a highly malignant tumor explaining recurrence of the tumor recurred after surgery. Cardiac angiosarcoma should be treated through a comprehensive treatment plan, comprising surgery, radiotherapy, and chemotherapy approaches.

Simultaneously Homogenized Electric Field and Ionic Flux for Reversible Ultrahigh-Areal-Capacity Li Deposition.

High areal capacity and stable Coulombic efficiency (CE) in lithium metal anodes (LMAs) play pivotal roles in developing high-energy-density rechargeable batteries. However, few reported LMAs delivering high and stable CE (>50 cycles) under ultrahigh areal capacity (>10 mA h cm-2). We demonstrated that the simultaneous homogenization of electric field and Li ion flux by using self-supported and surface-oxidized 3D hollow porous copper fibers (3D-HPCFs) can greatly increase both the areal capacity and reversibility of Li deposition. Li can be easily confined inside the hollow porous fibers and within the interspaces among fibers without uncontrollable Li dendrites. The 3D-HPCF-based anode can be deeply cycled at high capacity of 15 mA h cm-2 with average CE of 98.87% for 53 cycles, enabling a practical cell to realize high capacity retentions at a surplus Li of 10%. This work provides a novel Li deposition-regulation technology in LMAs targeting for next generation high-energy-density batteries.

Simple and sensitive method for the analysis of 14 antituberculosis drugs using liquid chromatography/tandem mass spectrometry in human plasma.

Monitoring plasma concentration and adjusting doses of antituberculosis (TB) drugs are beneficial for improving responses to drug treatment and avoiding adverse drug reactions. A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed to measure the plasma concentrations of 14 anti-TB drugs: ethambutol, isoniazid, pyrazinamide, levofloxacin, gatifloxacin, moxifloxacin, prothionamide, linezolid, rifampin, rifapentine, rifabutin, cycloserine, p-aminosalicylic acid, and clofazimine. METHODS: Human plasma was precipitated by acetonitrile and was subsequently separated by an AQ-C18 column with a gradient elution. Drug concentrations were determined using multiple reaction monitoring in positive ion electrospray ionization mode. According to pharmacokinetic data of patients, the peak concentration ranges and the timing of blood collection were determined. RESULTS: Intra- and interday precision was < 14.8%. Linearity, accuracy, extraction recovery, and matrix effect were acceptable for each drug. The stability of the method satisfied different storage conditions. CONCLUSIONS: The method allowed the sensitive and reproducible determination of 14 frequently used anti-TB drugs which has already been of benefit for some TB patients.

Operation for locally advanced cervical cancer after concurrent chemoradiotherapy.

OBJECTIVE: This paper aimed to discuss the scope of operation and clinical effects for locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively reviewed the records of 444 patients with stages IB2-IIB cervical cancer who were divided into two groups whether or not they received CCRT before radical operation in our institute from January 2013 to December 2016. Patients' characteristics, treatments, and outcomes were analyzed. RESULTS: The total efficiency (CR + PR) of the CCRT + operation group was 96.2%. Specifically, the CR rate was 9.1%, and the PR rate was 87.1%. The positive rates of cervical deep interstitial infiltration, lymphatic metastasis, and lymphangial infiltration of the operation group were significantly higher than those of the CCRT + operation group (P < 0.05). A total of 24 and 162 patients in the CCRT + operation group and the operation group, respectively, received adjuvant therapy (P < 0.05). The incidence rate of edema of the lower extremity, radiation enteritis, and radiocystitis after postoperative adjuvant radiotherapy in the operation group was significantly higher than that of the CCRT + operation group (P < 0.05). The 5-year survival rates and 5-year progression-free survival (PFS) rates of the CCRT + operation and operation groups were 79.3% versus 64.0% and 68.9% versus 45.2%, respectively (P < 0.05). CONCLUSIONS: Comprehensive treatment that combines CCRT and radical operation to LACC achieves satisfying clinical effects without increasing the occurrence rate of intraoperative and postoperative complications. Moreover, such treatment can improve the 5-year PFS rate and OS rate.

A Directional Strain Sensor Based on Anisotropic Microhoneycomb Cellulose Nanofiber-Carbon Nanotube Hybrid Aerogels Prepared by Unidirectional Freeze Drying.

Aerogels are one of the most popular composite reinforcement materials because of their high porosity and their continuous and homogeneous network. Most aerogels are isotropic, thus leading to isotropic composites when they are used as fillers. This fundamentally limits their applications in areas where anisotropy is needed. Here, an anisotropic microhoneycomb cellulose nanofiber- (CellF)-carbon nanotube (CNT) aerogel (denoted MCCA) is reported that contains unidirectionally aligned penetrating microchannels, which is prepared by a unidirectional freeze-drying method, using the structure-directing function of the CellFs. Due to its anisotropic nature, MCCA-reinforced polydimethylsilexane (denoted MCCA/PDMS) shows distinct anisotropic behavior, with the electrical conductivity and Young's modulus along the direction of penetrating microchannels being approximately twice those in the orthogonal direction. MCCA/PDMS is used to make "directional" strain sensors with electrical resistance as the output signal. They demonstrate a 92% sensitivity difference between the microchannel direction and its orthogonal direction. This approach can be used to prepare anisotropic MCCA-based composites with other polymers for different applications.

Alleviative Effects of C60 on the Trophic Transfer of Cadmium along the Food Chain in Aquatic Environment.

C60 could enhance the accumulation of pollutants in organisms, but their effects on higher trophic levels remain unknown. In the present study, the transfer of C60 from Daphnia magna to zebrafish (Danio rerio) and its effects on Cd transfer were investigated. The results showed that C60 could be transferred from D. magna to zebrafish through dietary exposure and accumulate mainly in the intestines, but biomagnification was not observed. The presence of C60 promoted accumulation of Cd in D. magna. However, it decreased Cd burden in the higher trophic level (zebrafish), displaying an alleviative effect on the trophic transfer of Cd along the food chain. To explore the underlying mechanisms, the release of Cd from D. magna in digestive fluids and changes in zebrafish digestive physiology were further investigated. The results showed that C60 did not inhibit Cd release from D. magna, but stimulated the digestive tracts of zebrafish to excrete Cd earlier and in a greater amount, which consequently lowered assimilation efficiency of Cd in zebrafish. Overall, the present study showed the trophic transfer of C60 in the aquatic food chain and revealed the effects of C60 on trophic transfer of Cd along the food chain in aquatic environment.

Randomized controlled trial comparing short-term outcomes of laparoscopic and open spleen-preserving splenic hilar lymphadenectomy for advanced proximal gastric cancer: An interim report.

BACKGROUND AND OBJECTIVES: We compared the clinical outcomes of laparoscopic and open spleen-preserving splenic hilar lymphadenectomy (LSPL and OSPL) for gastric cancer. METHODS: We performed a single-center, randomized, controlled trial to compare the short-term surgical outcomes between LSPL and OSPL. The study was registered in ClinicalTrials.gov (NCT02980861). RESULTS: A total of 222 patients were enrolled (114 in the LSPL group and 108 in the OSPL group). There were no significant differences between the two groups in operative time (P = 0.152), a number of harvested lymph nodes (P = 0.669) including no. 10 lymph nodes (2.1 ± 1.4 vs 2.3 ± 1.2, P = 0.713). The time taken for no. 10 lymph node dissection was similar in both groups (13.9 ± 10.4 vs 15.2 ± 9.4 minutes, P = 0.217); however, the LSPL group experienced less total blood loss (P < 0.001) and less blood loss during no. 10 lymph node dissection compared with the OSPL group (15.3 ± 37.8 vs 29.5 ± 36.4 mL, P < 0.001). The postoperative complication rates of LSPL and OSPL were 18.3% and 16.1%, respectively (P = 0.331). CONCLUSION: LSPL is a safe and feasible surgical procedure in no. 10 LN dissection for patients with advanced proximal gastric cancer. Thus, this prospective trial is continuing.

Effects of Carbon Quantum Dots on Aquatic Environments: Comparison of Toxicity to Organisms at Different Trophic Levels.

Carbon quantum dots (CQDs) have high hydrophilicity, high cell permeability, and are frequently used in water-based and biorelated applications, yet studies concerning the ecological risks of CQDs in aquatic environments are largely insufficient. In the present study, the toxicity of CQDs to zebrafish ( Danio rerio), zooplankton ( Daphnia magna), and phytoplankton ( Scenedesmus obliquus) were assessed for the first time. The results indicated that CQDs (up to 200 mg/L) could be depurated by D. rerio with negligible toxicity. In comparison, CQDs induced mortality and immobility in D. magna with a 48-h EC50 value and LC50 value of 97.5 and 160.3 mg/L, respectively. In S. obliquus, CQDs inhibited photosynthesis and nutrition absorption in a dose- and time-dependent manner, and the growth of algae was also inhibited with a 96-h EC50 value of 74.8 mg/L, suggesting that S. obliquus, the lowest trophic level in this study, was most sensitive to CQDs exposure. Further investigations revealed that CQDs induced an increase in oxidative stress in algae cells and a decrease in pH value of an algae medium, indicating that oxidative stress and water acidification may be the mechanisms underlying the toxicity of CQDs to S. obliquus.

Dysbindin as a novel biomarker for pancreatic ductal adenocarcinoma identified by proteomic profiling.

Pancreatic adenocarcinoma (PDAC) is known to have a poor prognosis partly because of lack of effective biomarkers. In the test set, we investigated dysbindin (DTNBP1) as a potential biomarker for PDAC by comparing preoperative and postoperative serum mass spectrometry (MS) proteomic profilings. Of the included 50 PDAC patients, 42 (positivity of 84.0%) detected a lower MS peak in postoperative serums than preoperative ones which was then identified as dysbindin. In the verification set, receiver operating characteristics (ROC) were used to assess diagnostic efficiency. 550 participants were included in the verification set [250 with PDAC, 80 with benign biliary obstruction (BBO), 70 with chronic pancreatitis (CP) and 150 healthy donors (HD)]. Dysbindin was increased in PDAC patient sera than in all controls. ROC curves revealed the optimum diagnostic cutoff for dysbindin was 699.16 pg/ml [area under curve (AUC) 0.849 (95% CI 0.812-0.885), sensitivity 81.9% and specificity 84.7%]. Raised concentration of dysbindin in sera could differentiate PDAC from BBO, CP and HD. Moreover, dysbindin maintained its diagnostic accuracy for PDAC patients who were CA19-9 negative [AUC 0.875 (95% CI 0.804-0.945), sensitivity 83.0%, specificity 89.0%] and for patients with benign biliary obstruction [AUC 0.849 (95% CI 0.803-0.894), sensitivity 82.3%, specificity 84.0%].Our discovery of dysbindin may complement measurement of CA19-9 in the diagnosis of PDAC and help to discriminate PDAC from other pancreatic diseases or begin biliary obstruction.

VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy.

Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) have potential applications in the treatment of fragile X syndrome, levodopa-induced dyskinesia in Parkinson disease, Alzheimer disease, addiction, and anxiety; however, clinical and preclinical studies raise concerns that complete blockade of mGlu5 and inverse agonist activity of current mGlu5 NAMs contribute to adverse effects that limit the therapeutic use of these compounds. We report the discovery and characterization of a novel mGlu5 NAM, N,N-diethyl-5-((3-fluorophenyl)ethynyl)picolinamide (VU0477573) that binds to the same allosteric site as the prototypical mGlu5 NAM MPEP but displays weak negative cooperativity. Because of this weak cooperativity, VU0477573 acts as a "partial NAM" so that full occupancy of the MPEP site does not completely inhibit maximal effects of mGlu5 agonists on intracellular calcium mobilization, inositol phosphate (IP) accumulation, or inhibition of synaptic transmission at the hippocampal Schaffer collateral-CA1 synapse. Unlike previous mGlu5 NAMs, VU0477573 displays no inverse agonist activity assessed using measures of effects on basal [(3)H]inositol phosphate (IP) accumulation. VU0477573 acts as a full NAM when measuring effects on mGlu5-mediated extracellular signal-related kinases 1/2 phosphorylation, which may indicate functional bias. VU0477573 exhibits an excellent pharmacokinetic profile and good brain penetration in rodents and provides dose-dependent full mGlu5 occupancy in the central nervous system (CNS) with systemic administration. Interestingly, VU0477573 shows robust efficacy, comparable to the mGlu5 NAM MTEP, in models of anxiolytic activity at doses that provide full CNS occupancy of mGlu5 and demonstrate an excellent CNS occupancy-efficacy relationship. VU0477573 provides an exciting new tool to investigate the efficacy of partial NAMs in animal models.

MicroRNA-15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development.

MicroRNAs (miRNAs) are important regulators of mouse brain development. However, their precise roles in this context remain to be elucidated. Through screening of expression profiles from a miRNA microarray and experimental analysis, we show here that miR-15b controls several aspects of cortical neurogenesis. miR-15b inhibits cortical neural progenitor cell (NPC) proliferation and promotes cell-cycle exit and neuronal differentiation. Additionally, miR-15b expression decreases the number of apical progenitors and increases basal progenitors in the VZ/SVZ. We also show that miR-15b binds to the 3' UTR of TET3, which plays crucial roles during embryonic development by enhancing DNA demethylation. TET3 promotes cyclin D1 expression, and miR-15b reduces TET3 expression and 5hmC levels. Notably, TET3 expression rescues miR-15b-induced impaired NPC proliferation and increased cell-cycle exit in vivo. Our results not only reveal a link between miRNAs, TET, and DNA demethylation but also demonstrate critical roles for miR-15b and TET3 in maintaining the NPC pool during early neocortical development.

Autophagy-related gene Atg5 is essential for astrocyte differentiation in the developing mouse cortex.

Astrocyte differentiation is essential for late embryonic brain development, and autophagy is active during this process. However, it is unknown whether and how autophagy regulates astrocyte differentiation. Here, we show that Atg5, which is necessary for autophagosome formation, regulates astrocyte differentiation. Atg5 deficiency represses the generation of astrocytes in vitro and in vivo. Conversely, Atg5 overexpression increases the number of astrocytes substantially. We show that Atg5 activates the JAK2-STAT3 pathway by degrading the inhibitory protein SOCS2. The astrocyte differentiation defect caused by Atg5 loss can be rescued by human Atg5 overexpression, STAT3 overexpression, and SOCS2 knockdown. Together, these data demonstrate that Atg5 regulates astrocyte differentiation, with potential implications for brain disorders with autophagy deficiency.

Enhanced sensing performance of supported graphitic carbon nitride nanosheets and the fabrication of electrochemiluminescent biosensors for IgG.

The key challenge for fabricating electrogenerated chemiluminescence (ECL) biosensors still lies in the improvement of the sensing performance of ECL luminophores. Graphite-like carbon nitride (g-C3N4) nanosheets were prepared and the cathodic ECL performance was investigated. The ECL emission of g-C3N4 nanosheets was greatly enhanced and higher sensing sensitivity towards copper ions was achieved by a "space effect", the incorporation of g-C3N4 nanosheets into a top-down prepared nanoporous matrix. Label-free ECL immunosensors were fabricated based on this simple sensing platform. The unique signal amplification strategy and simple fabrication procedure guarantee the sensor stability and production reproducibility. Nanoporous matrix supported ECL probes have potential as a versatile sensing strategy for the fabrication of ECL biosensors.