In-Sb Covalent Bonds over Sb2Se3/In2Se3 Heterojunction for Enhanced Photoelectrochemical Water Splitting.

Antimony selenide is a promising P-type photocatalyst, but it has a large number of deep energy level defects, leading to severe carrier recombination. The construction of a heterojunction is a common way to resolve this problem. However, the conventional heterojunction system inevitably introduces interface defects. Herein, we employ in situ synthesis to epitaxially grow In2Se3 nanosheets on Sb2Se3 nanorods and form In-Sb covalent interfacial bonds. This petal-shaped heterostructure reduced interface defects and enhanced the efficiency of carrier separation and transport. In this work, the photocurrent density in the proposed Sb2Se3/In2Se3 photocathode is 0.485 mA cm-2 at 0 VRHE, which is 30 times higher than that of pristine Sb2Se3 and it has prominent long-term stability for 24 h without obvious decay. The results reveal that the synergy of the bidirectional built-in electric field constructed between In2Se3 and Sb2Se3 and the solid In-Sb interfacial bonds together build a high-efficiency transport channel for the photogenerated carriers that display enhanced photoelectrochemical (PEC) water-splitting performance. This work provides efficient guidance for reducing interface defects via the in situ synthesis and construction of interfacial bonds.

Golgi-to-ER retrograde transport prevents premature differentiation of Drosophila type II neuroblasts via Notch-signal-sending daughter cells.

Stem cells are heterogeneous to generate diverse differentiated cell types required for organogenesis; however, the underlying mechanisms that differently maintain these heterogeneous stem cells are not well understood. In this study, we identify that Golgi-to-endoplasmic reticulum (ER) retrograde transport specifically maintains type II neuroblasts (NBs) through the Notch signaling. We reveal that intermediate neural progenitors (INPs), immediate daughter cells of type II NBs, provide Delta and function as the NB niche. The Delta used by INPs is mainly produced by NBs and asymmetrically distributed to INPs. Blocking retrograde transport leads to a decrease in INP number, which reduces Notch activity and results in the premature differentiation of type II NBs. Furthermore, the reduction of Delta could suppress tumor formation caused by type II NBs. Our results highlight the crosstalk between Golgi-to-ER retrograde transport, Notch signaling, stem cell niche, and fusion as an essential step in maintaining the self-renewal of type II NB lineage.

Calcitriol Attenuates HRV-Induced Respiratory Injury through the AMPK-mTOR-ER Stress Signaling Pathway.

Human rhinovirus (HRV) infection is one of the main causes of respiratory injury. Recently, calcitriol has been reported to have protective effect against respiratory infections. In this paper, we aimed to explore the effects and mechanisms of calcitriol on HRV-induced respiratory infection. Participants including pediatric patients diagnosed with HRV-induced respiratory infection (n = 50) and paired healthy controls (n = 40) were recruited at the Weifang People's Hospital between May 2019 and May 2020. The serum 25(OH)D3 level was measured in participants using ELISA kit. The HRV-induced respiratory infection model in human nasal mucosal epithelial cells (hNECs) was adapted, in vitro. HRV infection was measured by real-time PCR analysis of HRV expression. After HRV infection and treatment with calcitriol, the changes of cell viability were detected by MTT assay, the expression of ER stress-induced apoptosis and AMPK-mTOR related proteins by western blot, and the cell apoptosis by flow cytometry assay. In order to confirm whether AMPK-mTOR signal pathway was involved in the ER stress-induced apoptosis of hNECs, cells were pretreated with compound C which was a AMPK inhibitor. The 25-(OH)D3 concentration in serum collected in HRV-infected children was lower than that in controls. In vitro experiments showed that HRV infection decreased cell viability, and this effect was reversed when treated with calcitriol. Additionally, HRV increased levels of apoptosis and ER stress markers (including cleaved-caspase3, Bax, CHOP, nATF6, and BiP), while calcitriol significantly reversed these effects. Furthermore, calcitriol played a protective role by increasing p-AMPK and decreasing p-mTOR level. However, the protective effects of calcitriol could be abolished by compound C. Calcitriol protected HRV-infected hNECs by inhibiting the ER stress-induced apoptosis through the AMPK-mTOR signaling pathway. These protective effects of calcitriol against HRV-induced respiratory infection may provide an experimental basis for the clinical application.

LncRNA H19 Inhibits Proliferation and Migration of Airway Smooth Muscle Cells Induced by PDGF-BB Through miR-21/PTEN/Akt Axis.

BACKGROUND: LncRNA H19 expression is down-regulated in patients with asthma. The hyperplasia of airway smooth muscle cells (ASMCs) promotes the development of airway remodeling in asthma. Therefore, we attempted to evaluate the regulatory function of H19 in the proliferation and migration of ASMCs. METHODS: The expressions of H19 and miR-21 were detected using qRT-PCR. PDGF-BB-induced abnormal proliferation and migration of ASMCs was used as the airway remodeling model in vitro. The expressions of H19 and miR-21 were modified by transfection with pcDNA3.1-H19 and miR-21 mimic, respectively. CCK-8 assay, flow cytometry-based cell cycle analysis was conducted to examine the proliferation ability of ASMCs. The migration ability was measured by transwell assay. Dual-luciferase reporter system was carried out to find the potential relationship between miR-21 and H19 or PTEN. Western blot was conducted to detect the expressions of PCNA, MMP-9, α-SMA, PTEN, and the phosphorylation level of Akt. RESULTS: LncRNA-H19 expression was decreased and microRNA-21 expression was increased in serum samples of children with asthma and PDGF-BB-stimulated ASMCs. Overexpression of H19 reduced the proliferation and migration ability of ASMCs with PDGF-BB treatment and these changes were reversed by miR-21 mimic. H19 promoted the protein level of PTEN via sponging miR-21. Overexpression of H19 suppressed miR-21-induced phosphorylation of Akt, and the suppression effect of H19 on phosphorylation of Akt was significantly reduced after transfecting shPTEN in ASMCs. CONCLUSION: In this study, overexpression of H19 suppressed the proliferation and migration of ASMCs induced by PDGF-BB via miR-21/PTEN/Akt axis, which could be a potential biomarker and target for treating hyperplasia of airway smooth muscle cells.

EGFR-TKI-based vs non-EGFR-TKI-based adjuvant therapy in resected non-small-cell lung cancer with EGFR mutations: a meta-analysis of randomized controlled trials.

PURPOSE: The great efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has been identified in patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, it has not yet been established in postoperative adjuvant therapy. PATIENTS AND METHODS: To compare the prognosis and toxicity of EGFR-TKI-based adjuvant therapy and non-EGFR-TKI-based adjuvant therapy in resected NSCLC with sensitive EGFR mutations, we performed this meta-analysis of all eligible randomized controlled trials (RCTs). RESULTS: A comprehensive literature search of electronic databases (from inception to December 31, 2017) was performed. Additionally, abstracts presented at the American Society of Clinical Oncology conferences and World Conference on Lung Cancer held between January 2000 and November 2017 were searched to identify relevant trials. Disease-free survival (DFS), overall survival (OS), and grade 3 or 4 toxicities were analyzed. Five RCTs were selected, and 560 participants were included. This meta-analysis demonstrated that EGFR-TKI-based adjuvant therapy was associated with better DFS compared with non-EGFR-TKI-based therapy (HR =0.52, 95% CI 0.34-0.78, P=0.002). Pooled estimate has showed the trend of superiority of EGFR-TKI-based therapy in the aspect of OS (HR =0.65, 95% CI 0.22-1.91, P=0.43); however, the difference was not significant. The incidence rate of grade 3-4 toxicities of EGFR-TKI-based regimens was significantly higher for rash (OR =10.17, 95% CI 2.37-43.63, P=0.002) but lower for vomiting (OR =0.08, 95% CI 0.01-0.61, P=0.02). CONCLUSION: EGFR-TKI-based therapy was associated with better DFS compared with non-EGFR-TKI-based adjuvant therapy in patients with NSCLC harboring EGFR mutations. A trend was found that EGFR-TKI-based regimen improved the OS, though the difference was not significant. Although more OS data are needed, EGFR-TKI-based treatment has the potential to be an alternative of adjuvant therapy for NSCLC with a sensitive EGFR mutation.

The effects of GLP-1 analogues on pre-diabetes of the children.

The aim of the study was to evaluate the clinical efficacy of glucagon-like peptide-1 (GLP-1) analogues in children of pre-diabetes to delay or reverse the development of pre-diabetes into the state of diabetes by early intervention. Prospective and randomized controlled clinical trials were performed in 42 cases of newly diagnosed pre-diabetes in children. The sample size was randomly divided into the two groups. The first group included 21 subjects comprising the lifestyle intervention group, i.e., control group, and the second group included 21 subjects comprising the lifestyle intervention+GLP-1 analogues liraglutide group, i.e., observation group. Interventions carried out lasted 3 months. A review of intervention was carried out at 1 month and after 3 months. Medical examinations were carried out at the the time following diagnosis with pre-diabetes and after the intervention of 3 months. The medical test examinations included the fasting blood glucose (FPG), 2-hour postprandial blood glucose (2hPG), detection of glycated hemoglobin A1c (HbA1C), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), insulin resistance (IR) and the islet cell functions. After 1 month of intervention, the observation group exhibited a better control on FPG and 2hPG compared with the control group (P<0.05). After 3 months of the intervention, FPG and 2hPG levels of the observation group were significantly lower than those of the control group (P<0.01). The levels of HbA1C, TC, TG, LDL-C, HDL-C, and BMI of the observation group were statistically better controlled, when compared with the control group after the intervention of 3 months. The IR index of the observation group was significantly decreased compared to that of the control group (P<0.05) and the islet function index of the ß-cell of the observation group showed statistically higher values than that of the control group (P<0.05). In conclusion, GLP-1 analogues are a better regulator of blood sugar levels, effectively improve lipid profile, body mass, IR and islet ß-cell function. Furthermore, GLP-1 analogues opens up a new way to intervene pre-diabetes in children.

Complete mitochondrial genome of Allognosta vagans (Diptera, Stratiomyidae).

The complete mitochondrial genome (mitogenome) of Allognosta vagans (Loew, 1873) has been reported in this study. This is the first sequenced mitogenome of the subfamily Beridinae. The genome is 15,982 bp in length, including 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a partial sequence of the AT-rich region, and the AT-rich region contains several characteristic repeated sequences. In addition, the nucleotide composition of the coding region was 38.8% of A, 38.7% of T, 9.4% of C, 13.1% of G, 77.5% of A + T content. So far, five complete mitochondrial genome data of related species are available in our lab, all of them are used in Maximum Likelihood and Neighbour-Join analyses. The result supported that Xylomyidae and Stratiomyidae are sister group.

Alleviating salt stress in tomato seedlings using Arthrobacter and Bacillus megaterium isolated from the rhizosphere of wild plants grown on saline-alkaline lands.

Salt-induced soil degradation is common in farmlands and limits the growth and development of numerous crop plants in the world. In this study, we isolated salt-tolerant bacteria from the rhizosphere of Tamarix chinensis, Suaeda salsa and Zoysia sinica, which are common wild plants grown on a saline-alkaline land, to test these bacteria's efficiency in alleviating salt stress in tomato plants. We screened out seven strains (TF1-7) that are efficient in reducing salt stress in tomato seedlings. The sequence data of 16S rRNA genes showed that these strains belong to Arthrobacter and Bacillus megaterium. All strains could hydrolyze casein and solubilize phosphate, and showed at least one plant growth promotion (PGP)-related gene, indicating their potential in promoting plant growth. The Arthrobacter strains TF1 and TF7 and the Bacillus megaterium strain TF2 and TF3 could produce indole acetic acid under salt stress, further demonstrating their PGP potential. Tomato seed germination, seedling length, vigor index, and plant fresh and dry weight were enhanced by inoculation of Arthrobacter and B. megaterium strains under salt stress. Our results demonstrated that salt-tolerant bacteria isolated from the rhizosphere of wild plants grown on saline-alkaline lands could be used for alleviating salt stress in crop plants.

PKA turnover by the REGγ-proteasome modulates FoxO1 cellular activity and VEGF-induced angiogenesis.

The REGγ-proteasome serves as a short-cut for the destruction of certain intact mammalian proteins in the absence of ubiquitin- and ATP. The biological roles of the proteasome activator REGγ are not completely understood. Here we demonstrate that REGγ controls degradation of protein kinase A catalytic subunit-α (PKAca) both in primary human umbilical vein endothelial cells (HUVECs) and mouse embryonic fibroblast cells (MEFs). Accumulation of PKAca in REGγ-deficient HUVECs or MEFs results in phosphorylation and nuclear exclusion of the transcription factor FoxO1, indicating that REGγ is involved in preserving FoxO1 transcriptional activity. Consequently, VEGF-induced expression of the FoxO1 responsive genes, VCAM-1 and E-Selectin, was tightly controlled by REGγ in a PKA dependent manner. Functionally, REGγ is crucial for the migration of HUVECs. REGγ(-/-) mice display compromised VEGF-instigated neovascularization in cornea and aortic ring models. Implanted matrigel plugs containing VEGF in REGγ(-/-) mice induced fewer capillaries than in REGγ(+/+) littermates. Taken together, our study identifies REGγ as a novel angiogenic factor that plays an important role in VEGF-induced expression of VCAM-1 and E-Selectin by antagonizing PKA signaling. Identification of the REGγ-PKA-FoxO1 pathway in endothelial cells (ECs) provides another potential target for therapeutic intervention in vascular diseases.

Site-specific acetylation of the proteasome activator REGγ directs its heptameric structure and functions.

The proteasome activator REGγ has been reported to promote degradation of steroid receptor coactivator-3 and cyclin-dependent kinase inhibitors p21, p16, and p19 in a ubiquitin- and ATP-independent manner. A recent comparative analysis of REGγ expression in mouse and human tissues reveals a unique pattern of REGγ in specific cell types, suggesting undisclosed functions and biological importance of this molecule. Despite the emerging progress made in REGγ-related studies, how REGγ function is regulated remains to be explored. In this study, we report for the first time that REGγ can be acetylated mostly on its lysine 195 (Lys-195) residue by CREB binding protein (CBP), which can be reversed by sirtuin 1 (SIRT1) in mammalian cells. Site-directed mutagenesis abrogated acetylation at Lys-195 and significantly attenuated the capability of REGγ to degrade its target substrates, p21 and hepatitis C virus core protein. Mechanistically, acetylation at Lys-195 is important for the interactions between REGγ monomers and ultimately influences REGγ heptamerization. Biological analysis of cells containing REGγ-WT or REGγ-K195R mutant indicates an impact of acetylation on REGγ-mediated regulation of cell proliferation and cell cycle progression. These findings reveal a previously unknown mechanism in the regulation of REGγ assembly and activity, suggesting a potential venue for the intervention of the ubiquitin-independent REGγ proteasome activity.

Facial expression recognition: can preschoolers with cochlear implants and hearing aids catch it?

Tager-Flusberg and Sullivan (2000) presented a cognitive model of theory of mind (ToM), in which they thought ToM included two components--a social-perceptual component and a social-cognitive component. Facial expression recognition (FER) is an ability tapping the social-perceptual component. Previous findings suggested that normal hearing children did not demonstrate any advantage over those with cochlear implants (CI) or hearing aids (HA) in FER with age and gender matched. In these studies, the ages of the participants with CI or HA were over 7 years old. However, normal hearing preschoolers can accurately recognize basic facial expressions. Children's early FER skills are essential to later successful social interactions. It is not clear whether preschoolers with CI or HA have problems in FER. Two experiments were conducted to compare the FER of preschoolers with CI or HA with normal hearing children (with age matched). The results of both experiments consistently showed that normal hearing children performed significantly better than those with CI or HA, suggesting to some extent that there was a delay in preschoolers with CI or HA on FER. No significant correlations (with age and type of participants controlled) were found between language ability (measured by PPVT) and FER in Experiment 2, to some extent validating a cognitive model of ToM in another view. The findings suggested that earlier rehabilitation for children with CI or HA should include not only language treatment but also emotional intervention, which would help them catch up with normal hearings as soon as possible.