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FGFR3 activating mutations and abnormal expression are linked to tumor development. However, the current state of research on FGFR3 gene expression regulation is relatively insufficient. In this study, we have reported that the FGFR3 promoter's positive strand contains several G-tracts and most likely forms a G-quadruplex (G4) structure. Circular dichroism investigations revealed that oligonucleotides from this region exhibit G-quadruplex-like molar ellipticity. We further validated the G4 structure of the FGFR3 promoter using biochemical and cellular molecular biology techniques. The G-quadruplex mutation enhanced the transcriptional activity of the FGFR3 promoter and DNA replication, suggesting that the G4 structure inhibits its expression. Furthermore, we conducted a preliminary screen for helicases associated with FGFR3 expression and explored their regulatory effects on FGFR3 gene transcription. Subsequently, we investigated the effect of curcumin on the stability of the G4 structure of the FGFR3 promoter and its regulatory effect on FGFR3 expression. • 1.The positive strand of the FGFR3 promoter contains several G-tracts with the capacity to form G-quadruplex structures. • The G-quadruplex negatively regulates FGFR3 promoter-mediated transcription and its DNA replication. • Helicases DDX42 and RTEL1 potentially unwind the G4 structures in the FGFR3 promoter. • Curcumin binds to and stabilizes the FGFR3 promoter G-quadruplexes and inhibits its transcriptional activity. [ABSTRACT FROM AUTHOR]

The purpose of this research is to identify the best edible fungi among eight species of edible fungi, and to study the best enzymatic hydrolysis reaction conditions in order to enhance the umami taste of edible fungi. The free 5'-nucleotides and amino acids in eight kinds of edible fungi were determined by high performance liquid chromatography (HPLC), and the equivalent umami concentration (EUC) values were calculated. Combined with the sensory evaluation, it was found that the EUC value of Agaricus bisporus was the highest, which was 826.551±20.057 g/100 g, and with a good umami taste. Enzymatic hydrolysis was conducted to further release umami substances in edible fungi, and the best effect was found under the enzyme mixtures of cellulase and Protamex™ by EUC values and sensory evaluation. Through the single-factor experiments and orthogonal tests, taking EUC value, sensory evaluation, degree of hydrolysis and soluble solids content as indexes, the optimal conditions for enzymatic hydrolysis were at 50°C, a solid-liquid ratio of 1:10, a pH of 5.5, a total enzyme mixtures addition of 4000 U/g, and a cellulase hydrolysis time of 60 min followed by the addition of a Protamex™ hydrolysis for 150 min. The final enzymatic hydrolysate had an intensive saltiness and umami taste with an EUC value of 1619.05±3.38 g/100 g. [Display omitted] • Agaricus bisporus had the highest EUC value and the best umami taste. • The compound enzymolysis of cellulase and Protamex™ showed the best effect on the umami extraction of Agaricus bisporus. • Soluble solids, EUC, sensory evaluation and DH were used as indexes. [ABSTRACT FROM AUTHOR]

TP53INP2 (tumor protein p53-inducible nuclear protein 2), known as an autophagy protein, is essential for regulating transcription and starvation-induced autophagy, which plays a crucial role in the oncogenesis and progression of various cancers. The present study aims to investigate the expression pattern, function and prognostic value of TP53INP2 in colorectal cancer (CRC). Here, we report that low expression of TP53INP2 correlates with poor survival in CRC patients. TP53INP2 was significantly downregulated in CRC tissues compared with adjacent tissues. As the malignancy of CRC progresses, the expression level of TP53INP2 gradually decreased. Knockdown of TP53INP2 promoted CRC cell proliferation and tumor growth in mice. Mechanistically, TP53INP2 deficiency decreased phosphorylation of β-catenin on S33, S37, and T41, resulting in increased accumulation of β-catenin and enhanced nuclear translocation and transcriptional activity. Moreover, we further demonstrated that TP53INP2 sequestered TIM50, thereby inhibiting its activation of β-catenin. Taken together, our findings indicate that the downregulation of TP53INP2 promotes CRC progression by activating β-catenin and suggest that TP53INP2 may be a candidate therapeutic target for CRC. • Low TP53INP2 expression is associated with poor prognosis in colorectal cancer. • Loss of TP53INP2 function decreases phospho-S33/S37/T41 β-catenin, leading to CRC proliferation and tumor progression. • TP53INP2 sequesters TIM50 to inhibit its activation of β-catenin. • TP53INP2 could be used as a marker for diagnosis and treatment of highly malignant colorectal cancer. [ABSTRACT FROM AUTHOR]

Interleukin-17A (IL-17A) is a soluble pro-inflammatory cytokine, which is mainly secreted by Th17 cells. In humans, IL-17A mRNA and protein levels are increased in several autoimmune diseases, including psoriasis and rheumatoid arthritis. This study describes the preclinical in vitro and in vivo characterization of GR1501, a human IL-17A-neutralizing IgG4 monoclonal antibody. GR1501 binds human, rhesus and cynomolgus IL-17A with high affinity but does not bind to mouse IL-17A or other IL-17 family members. GR1501 effectively blocks the interaction between IL-17A and its receptor IL-17RA, thereby inhibiting IL-17A-induced CXCL1 and IL-6 release in cells and mice. In mouse air pouch model, GR1501 effectively inhibits IL-17A induced leukocytes infiltration into the air pouch. GR1501 also reduces joint swelling and inflammation in mouse arthritis model. These data suggest that GR1501 is a potent and selective IL-17A-neutralizing monoclonal antibody and will support the clinical investigation of this monoclonal antibody in psoriasis and rheumatoid arthritis. • IL-17A is a potential target of treatment against psoriasis and rheumatoid arthritis. • GR1501 is a potent and selective IL-17A-neutralizing mAb. • GR1501 exhibits powerful functional activity both in vitro and in vivo. • The preclinical data presents here support the clinical investigation of GR1501 in psoriasis and rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

As an efficient wastewater pretreatment biotechnology, electrostimulated hydrolysis acidification (eHA) has been used to accelerate the removal of refractory pollutants, which is closely related to the effects of electrostimulation on microbial interspecies associations. However, the ecological processes underpinning such linkages remain unresolved, especially for the microbial communities derived from different niches, such as the electrode surface and plankton. Herein, the principles of cross-niche microbial associations and community assembly were investigated using molecular ecological network and phylogenetic bin-based null model analysis (iCAMP) based on 16S rRNA gene sequences. The electrostimulated planktonic sludge and electrode biofilm displayed significantly (P < 0.05) 1.67 and 1.53 times higher organic nitrogen pollutant (azo dye Alizarin Yellow R) degradation efficiency than non-electrostimulation group, and the corresponding microbial community composition and structure were significantly (P < 0.05) changed. Electroactive bacteria and functional degraders were enriched in the electrode biofilm and planktonic sludge, respectively. Notably, electrostimulation strengthened the synergistic microbial associations (1.8 times more links) between sludge and biofilm members. Additionally, both electrostimulation and cross-niche microbial associations induced greater importance of deterministic assembly. Overall, this study highlights the specificity of cross-electrode surface microbial associations and ecological processes with electrostimulation and advances our understanding of the manipulation of sludge microbiomes in engineered wastewater treatment systems. [Display omitted] • The electrostimulated sludge had obviously higher pollutant degradation efficiency. • Sludge community at different niche markedly shifted upon electrostimulation. • More microbial associations of cross-niche evolved upon electrostimulation. • Electrostimulation/cross-niche biotic factors contributed to deterministic assembly. [ABSTRACT FROM AUTHOR]

The APOBEC3 family of DNA cytosine deaminases is capable of restricting the replication of HIV-1 and other pathogens. Here, we report a 1.92 Å resolution crystal structure of the Vif-binding and catalytic domain of APOBEC3F (A3F). This structure is distinct from the previously published APOBEC and phylogenetically related deaminase structures, as it is the first without zinc in the active site. We determined an additional structure containing zinc in the same crystal form that allows direct comparison with the zinc-free structure. In the absence of zinc, the conserved active site residues that normally participate in zinc coordination show unique conformations, including a 90 degree rotation of His249 and disulfide bond formation between Cys280 and Cys283. We found that zinc coordination is influenced by pH, and treating the protein at low pH in crystallization buffer is sufficient to remove zinc. Zinc coordination and catalytic activity are reconstituted with the addition of zinc only in a reduced environment likely due to the two active site cysteines readily forming a disulfide bond when not coordinating zinc. We show that the enzyme is active in the presence of zinc and cobalt but not with other divalent metals. These results unexpectedly demonstrate that zinc is not required for the structural integrity of A3F and suggest that metal coordination may be a strategy for regulating the activity of A3F and related deaminases. [ABSTRACT FROM AUTHOR]

On January 3, 2019, Chang'E-4 (CE-4) probe successfully achieved soft landing on the farside of the Moon. A large number of small craters in the landing area can be found in the high-resolution remote sensing images. These small craters played a vital role in the evolution of lunar regolith because of the overturning and mixing of lunar surface material through excavating and ejecting during impact processes. However, the research of the gardening process by small craters and the evolution of farside lunar regolith are still insufficient. This research aims to make quantitative analysis to the evolution of the lunar regolith from regional small impacts and apply them in the CE-4 landing area. Firstly, the processes of excavation and ejection of a single small impact on the lunar surface are analyzed, during which the formation and distribution of lunar regolith are numerically modeled. Then, based on the remote sensing observation and the analysis of regional impact flux, a group of impact events with resulting lunar regolith are modeled by Monte Carlo method. Thirdly, the above analysis is applied in the CE-4 landing area, and the thickness, grain size distribution, and overturning times of the lunar regolith are calculated. Finally, the influencing factors are discussed and evolution process of lunar regolith is summarized. The results indicate that the formation of lunar regolith is controlled by larger impact events, while the surficial overturning and mixing of lunar regolith are mainly caused by smaller impact events. In addition, the lunar regolith is mostly formed in the earlier times because of the high impact flux at that time. For example, the absolute model age of the CE-4 landing area is about 3.5 Ga, while the lunar regolith had mostly been formed before 3.0 Ga and changed slowly afterwards. Our model beyond the observational capability of the Yutu-2's lunar penetrating radar (LPR), and the results can contribute to better understanding of the regional lunar regolith formation and evolution. • Lunar regolith evolution is quantitatively analyzed with the proposed EMSC. • Lunar regolith formation is mostly controlled by larger impact events. • Lunar regolith in CE-4 landing area is mainly formed before 3.0 Ga. [ABSTRACT FROM AUTHOR]

Freezing deteriorates the baking quality of frozen bread dough. This study revealed the protective effects of zein-based ice nucleation films (INFs) on the baking quality of frozen dough. INFs were prepared by immobilizing biogenic ice nucleators on the surface of zein films, which consequently revealed ice nucleation activity and increased the ice nucleation temperature of water from −15 °C to −6.7 °C. By using these films to wrap frozen dough during five freeze/thaw cycles, the specific volume of bread was increased by up to 25% compared to the bread from control frozen dough. The reason was attributed to 40% more viable yeast cells preserved by INFs. In addition, zein-based INFs also reduced the water loss by frozen dough resulting in higher water content in bread crumb. Combining the protective effects on both specific volume and water content from zein-based INFs, the obtained bread showed 68% lower firmness and fracturability and 2.4 times higher resilience compared to the control. The INFs were also superior in that for zein-based INFs, biogenic ice nucleators showed desirable affinity with the surface to sustain at least fifteen repetitive uses on freezing water. [ABSTRACT FROM AUTHOR]

Abstract: Freezing deteriorates the baking quality of frozen bread dough by causing lethal injury to yeast cells and depolymerization to the gluten network. To investigate the potential of biogenic ice nucleators in frozen food applications, the effect of extracellular ice nucleators (ECINs) from Erwinia herbicola on the baking quality of frozen dough upon three freeze/thaw cycles were investigated. With addition of ECINs to the activity of 2.4 × 106 units per gram of dough, hardening of bread crumb caused by three freeze/thaw cycles was alleviated by about 50% compared to the control. Additionally, the bread from frozen dough with added ECINs showed 50% larger specific volume compared to the control. The mechanism of cryoprotective effects from ECINs was possibly that ECINs helped in preserving the viability of yeast cells during freeze/thaw cycles. ECINs were able to improve the viability of log-phase and stationary-phase yeast cells in suspensions by about 100 and 10 fold, respectively, and viability of yeast in the frozen dough by 17%. This study revealed the potential of ECINs as a cryoprotectant for applications in the food and biotechnology industries. [Copyright &y& Elsevier]

Abstract: Polyinosinic acid has been known to adopt the four-stranded helical structure but its basic unit, inosine tetrad (I tetrad), has not been determined at the atomic level. Here we report the crystal structure of an RNA quadruplex containing an I tetrad at 1.4 Å resolution. The I tetrad has one cyclic hydrogen bond N1…O6 with the bond length of 2.7 Å. A water bridge is observed in the minor groove side of the base tetrad. Even though it is sandwiched by guanine tetrads (G tetrads), the I tetrad is buckled towards the 3′ side of the tetrad plane, which results from the different interaction strength with K ions on two sides of the tetrad plane. Comparison with both G tetrad and adenine tetrad indicates that lack of NH2 in the C2 position makes the I tetrad prone to buckle for interactions with ligands. Two U*(G-G-G-G) base pentads are observed at the junction of the 5′ termini of two quadruplexes. The uridine residue in the base pentad is engaged in two hydrogen bonding interactions (N2(G)-H…O2(U) and O2′(G)-H…O4(U)) and a water-mediated interaction (N3(G) and N3(U)) with the G tetrad. We also discuss the roles of amino group in purine tetrads and the inter-quadruplex interactions in RNA molecules. These quadruplexes may interact with each other by stacking, groove binding and intercalation. [Copyright &y& Elsevier]

As many as five members of the APOBEC3 family of DNA cytosine deaminases are capable of inhibiting HIV-1 replication by deaminating viral cDNA cytosines and interfering with reverse transcription. HIV-1 counteracts restriction with the virally encoded Vif protein, which forms a hybrid ubiquitin ligase complex that directly binds APOBEC3 enzymes and targets them for proteasomal degradation. APOBEC3H (A3H) is unique among family members by dimerization through cellular and viral duplex RNA species. RNA binding is required for localization of A3H to the cytoplasmic compartment, for efficient packaging into nascent HIV-1 particles and ultimately for effective virus restriction activity. Here we compared wild-type human A3H and RNA binding–defective mutants to ask whether RNA may be a factor in the functional interaction with HIV-1 Vif. We used structural modeling, immunoblotting, live cell imaging, and split green fluorescence protein (GFP) reconstitution approaches to assess the capability of HIV-1 Vif to promote the degradation of wild-type A3H in comparison to RNA binding–defective mutants. The results combined to show that RNA is not strictly required for Vif-mediated degradation of A3H, and that RNA and Vif are likely to bind this single-domain DNA cytosine deaminase on physically distinct surfaces. However, a subset of the results also indicated that the A3H degradation process may be affected by A3H protein structure, subcellular localization, and differences in the constellation of A3H interaction partners, suggesting additional factors may also influence the fate and functionality of this host-pathogen interaction. Image 1 • Vif degrades a subset of RNA binding–defective A3H mutants. • RNA-mediated A3H dimerization is not hindered by Vif. • Vif and RNA are likely to bind physically distinct surfaces of A3H. [ABSTRACT FROM AUTHOR]

The X-ray crystallographic structure of the mature form of subtilisin E-S7 (SES7) at 1.90 Å resolution is reported here. Structural comparisons between the previously reported propeptide-subtilisin E complex (1SCJ) and our mature form subtilisin E-S7 (6O44) provide insight into active site adjustments involved in catalysis and specificity. To further investigate the protease substrate selectivity mechanism, we used SES7 to hydrolyze skim milk and analyzed the hydrolysates by LC-MS for peptide identification. The cleavage pattern suggests a high preference for proline at substrate P2 position. The results based on the peptide analysis are consistent with our structural observations, which is instrumental in future protein engineering by rational design. Furthermore, the ACE-inhibitor and NLN-inhibitor activity of the hydrolysates were determined to assess the utility of SES7 for further industrial applications; IC 50 -ACE = 67 ± 0.92 μg/mL and IC 50 -NLN = 263 ± 13 μg/mL. • The key conformational flexibilities define SES7 specificity for U-shape substrate. • SES7 prefer proline at the substrate P2 position from LC/MS peptide profile. • Bioactive peptides with proline at the P2 position were also identified. • High ACE-inhibitory and NLN-inhibitory activity of SES7 hydrolysate were determined. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cryo-EM reveals HIV-2 immature particles hexamer organization to 5.5 Å. • Reconstruction map revealed a stable, wineglass-shaped Gag hexamer structure. • HIV-2 CA CTD crystal structure presents a helix 12 in the absence of SP1 residues. • Structural analysis of HIV-2 assembly and maturation provide insight to H10 and H12. • Cryo-ET demonstrates the occupancy of HIV-2 hexameric Gag lattice in 3D. Retrovirus immature particle morphology consists of a membrane enclosed, pleomorphic, spherical and incomplete lattice of Gag hexamers. Previously, we demonstrated that human immunodeficiency virus type 2 (HIV-2) immature particles possess a distinct and extensive Gag lattice morphology. To better understand the nature of the continuously curved hexagonal Gag lattice, we have used the single particle cryo-electron microscopy method to determine the HIV-2 Gag lattice structure for immature virions. The reconstruction map at 5.5 Å resolution revealed a stable, wineglass-shaped Gag hexamer structure with structural features consistent with other lentiviral immature Gag lattice structures. Cryo-electron tomography provided evidence for nearly complete ordered Gag lattice structures in HIV-2 immature particles. We also solved a 1.98 Å resolution crystal structure of the carboxyl-terminal domain (CTD) of the HIV-2 capsid (CA) protein that identified a structured helix 12 supported via an interaction of helix 10 in the absence of the SP1 region of Gag. Residues at the helix 10–12 interface proved critical in maintaining HIV-2 particle release and infectivity. Taken together, our findings provide the first 3D organization of HIV-2 immature Gag lattice and important insights into both HIV Gag lattice stabilization and virus maturation. [ABSTRACT FROM AUTHOR]

In the new era of global net zero, how to reduce carbon intensity became a hot topic, while few attentions had been paid to the impacts of casual environmental regulation, especially in the emerging economy such as China. In this regard, this study uses the panel data of 30 provinces in China from 2003 to 2019 to study the impacts of causal environmental regulation on the carbon intensity, with the adoption of multiple econometric models. The empirical results show that causal environmental regulation has a significant inhibitory effect on carbon intensity, while at current stage, causal environmental regulation cannot inhibit carbon intensity through the mediating of green innovation and renewable energy production. Fortunately, energy low-carbon reconstitution and industrial structure upgrading are proved to effectively act as the intermediary channels. In addition, the spatial spillover effects and the spatial heterogeneity are supported in the empirical analysis. In a summary, this study starts with the case of China to provide a realistic reference case for the international community, enriches the theory, policy and practice related to environmental regulation, and provides a realistic reference example for emerging economics in a developing country. • The carbon reduction effect of casual environmental regulation is investigated. • Dual intermediary channels in terms of energy and industry are proved effective. • Spatial spillover effects and the spatial heterogeneity are supported. [ABSTRACT FROM AUTHOR]

Anaplasma phagocytophilum , the bacterial pathogen responsible for tick-borne fever and human granulocytic anaplasmosis, can seriously affect the health of humans and a wide range of other mammals. In this study, we developed a recombinase polymerase amplification (RPA) assay to detect A. phagocytophilum in clinical samples. Following alignment of the relevant DNA sequences, a pair of specific primers based on the 16S rRNA gene was designed to specifically detect A. phagocytophilum. The assay was performed at a constant temperature of 38 °C for 30 min, with a final primer concentration of 0.4 μM. The specificity of the primers was confirmed when DNA from A. phagocytophilum was used as the positive control, and DNA from other related pathogens were used as the negative controls, with ddH 2 O acting as the blank control. The results showed that the primers did not cross-react with DNA from the other related pathogens. The assay's detection limit was 1.77 × 10−5 ng/μl, a 10 × higher sensitivity level than that determined for nested PCR. The RPA assay's performance was evaluated using 44 clinical samples, and the prevalence results for A. phagocytophilum were found to not differ significantly between the RPA assay and the nested PCR. Thus, we have developed a specific, sensitive, rapid and cost-effective RPA method, requiring only a water bath, for the detection of A. phagocytophilum. The assay should be especially useful in resource-limited areas where access to laboratory equipment is limited. Image 1 • RPA-based assay for detection of A. phagocytophilum was first developed. • The method could be completed better at 38 °C for 30 min. • The sensitivity of this method is 10 times higher than that of Nested PCR. • This method is more suitable for clinical application in resource-limited areas. [ABSTRACT FROM AUTHOR]

CRKL (CRK Like Proto-Oncogene) belongs to the Crk family and is a 39-kDa adapter protein that encodes SH2 and SH3 (src homologs) domains. To identify its oncogenic role in malignant melanoma, we investigated the association between CRKL and mutation, prognosis, tumor mutation burden, immune cell infiltration of melanoma, and explored the associations between CRKL and immunotherapy response. Our results showed that abnormal CRKL expression is associated with poor prognosis in melanoma and is significantly correlated with immune-activated pathways and processes, immune cell infiltrations, and expression of immunoregulators. Importantly, we found that CRKL expression is a predictive biomarker for anti-PD1 therapy response in melanoma patients. Furthermore, inhibiting CRKL expression in melanoma cell lines suppressed their proliferation and metastasis, as well as activated the pyroptosis-related pathway. Our study provides potential mechanisms of melanoma pathogenesis, which may suggest new avenues for targeted therapy in this disease. • This study comprehensively analyzed the role of CRKL in malignant melanoma, including its relationship with prognosis, epigenetic modifications, cancer stemness, immune regulation, and inflammatory pathways. • In addition to inhibiting proliferation and metastasis, our findings reveal a close association between CRKL and the NLRP3-GSDMD-caspase-1 dependent pyroptosis pathway. • CRKL expression accurately predicts the immune response of melanoma, and patients with low expression levels exhibit greater responsiveness to anti-PD1 therapy. [ABSTRACT FROM AUTHOR]

Anaerobic degradation is the major pathway for microbial degradation of benzene, toluene, ethylbenzene, and xylenes (BTEX) under electron acceptor lacking conditions. However, how exogenous electron acceptors modulate BTEX degradation through shaping the microbial community structure remains poorly understood. Here, we investigated the effect of various exogenous electron acceptors on BTEX degradation as well as methane production in anaerobic microbiota, which were enriched from the same contaminated soil. It was found that the BTEX degradation capacities of the anaerobic microbiota gradually increased along with the increasing redox potentials of the exogenous electron acceptors supplemented (WE: Without exogenous electron acceptors < SS: Sulfate supplement < FS: Ferric iron supplement < NS: Nitrate supplement), while the complexity of the co-occurring networks (e.g., avg K and links) of the microbiota gradually decreased, showing that microbiota supplemented with higher redox potential electron acceptors were less dependent on the formation of complex microbial interactions to perform BTEX degradation. Microbiota NS showed the highest degrading capacity and the broadest substrate-spectrum for BTEX, and it could metabolize BTEX through multiple modules which not only contained fewer species but also different key microbial taxa (eg. Petrimonas , Achromobacter and Comamonas). Microbiota WE and FS, with the highest methanogenic capacities, shared common core species such as Sedimentibacter , Acetobacterium , Methanobacterium and Smithella/Syntrophus , which cooperated with Geobacter (microbiota WE) or Desulfoprunum (microbiota FS) to perform BTEX degradation and methane production. This study demonstrates that electron acceptors may alter microbial function by reshaping microbial community structure and regulating microbial interactions and provides guidelines for electron acceptor selection for bioremediation of aromatic pollutant-contaminated anaerobic sites. • Proteobacteria and Methanobacterium were the key microbes to perform the function of microbiota. • Complexity of microbial interaction gradually decreased with the increasing redox potentials of electron acceptors. • Electron acceptors altered microbiota functions by reshaping and regulating microbial community structure. [ABSTRACT FROM AUTHOR]

Melatonin, a lipophilic molecule that is mainly synthesized in the pineal gland, performs various neuroprotective functions. However, the detailed role and mechanisms of promoting neuronal differentiation remains limited. This study demonstrated that 10 μM melatonin led to significant increases in the proliferation and neurite outgrowth of PC12 cells. Increased expression of microtubule-associated protein 2 (MAP2, a neuron-specific protein) was also observed. However, luzindole (melatonin receptor antagonist) and PD98059 (MEK inhibitor) attenuated these increases. LY294002 (AKT inhibitor) inhibited melatonin-mediated proliferation in PC12 cells and did not affect melatonin-induced neural differentiation. The expression of p-ERK1/2/ERK1/2 was increased by melatonin treatment for 14 days in PC12 cells, whereas luzindole or PD98059 reduced the melatonin-induced increase. These results suggest that the activation of both the MEK/ERK and PI3K/AKT signaling pathways could potentially contribute to melatonin-mediated proliferation, but that only the MEK/ERK pathway participates in the melatonin-induced neural differentiation of PC12 cells. Altogether, our study demonstrates for the first time that melatonin may exert a positive effect on neural differentiation via melatonin receptor signalling and that the MEK/ERK1/2 signalling may act down stream from the melatonin pathway. [ABSTRACT FROM AUTHOR]

Chang'e-5 (CE-5) mission, the first lunar sample return mission of China, landed in Northern Oceanus Procellarum (51.92°W, 43.06°N) on Dec. 1, 2020. The descent camera onboard the CE-5 lander collected hundreds of descent images during the landing process. These high-resolution images are used to generate high resolution digital orthophoto map (DOM) and digital elevation model (DEM), providing a data basis for the detailed analysis of the geology and topography of the landing area. Impact craters are the most common landforms on the Moon, and small craters measured from high resolution data are very important for understanding the impacting process and the properties of the lunar surface. In this research, we create a catalogue of small craters measured from the centimeter-resolution image mapping products in the CE-5 landing area, and most of the craters are smaller than 100 m in diameter. The distribution and morphological characteristics of the craters are analyzed, including the completeness diameter, the spatial density distribution and the relationship between depth and diameter. The mean depth-to-diameter ratio of 231 craters with diameters ranging from 7.0 to 371.2 m and depths ranging from 0.21 to 45.9 m in CE-5 landing area is ~0.055. This result indicate that our catalogue has slightly low d/D ratios compared with other larger craters and the small craters in Chang'e-4 landing area. • A catalogue of meter-scale craters in the Chang'e-5 landing area is created. • The distribution and morphological characteristics of this catalogue are analyzed in detail. • Small craters in this catalogue have a smaller d/D ratio of ~0.055. [ABSTRACT FROM AUTHOR]

Abstract: Acute stretch caused by volume overload (VO) of aorto-caval fistula (ACF) induces a variety of myocardial responses including mast cell accumulation, matrix metalloproteinase (MMP) activation, and collagen degradation, all of which are critical in dictating long-term left ventricle (LV) outcome to VO. Meanwhile, these responses can be part of myocardial inflammation dictated by tumor necrosis factor-α (TNF-α), which is elevated after acute ACF. However, it is unknown whether TNF-α mediates a major myocardial inflammatory response to stretch in early VO. In 24-h ACF and sham rats, microarray gene expression profiling and subsequent Ingenuity Pathway Analysis identified a predominant inflammatory response and a gene network of biologically interactive genes strongly linked to TNF-α. Western blot demonstrated increased local production of TNF-α in the LV (1.71- and 1.66-fold in pro- and active-TNF-α over control, respectively, P <0.05) and cardiomyocytes (2- and 4-fold in pro- and active-TNF-α over control, respectively, P <0.05). TNF-α neutralization with infliximab (5.5 mg/kg) attenuated the myocardial inflammatory response to acute VO, as indicated by inhibition of inflammatory gene upregulation, myocardial infiltration (total CD45+ cells, mast cells, and neutrophils), MMP-2 activation, collagen degradation, and cardiac cell apoptosis, without improving LV remodeling and function. These results indicate that TNF-α produced by cardiomyocytes mediates a predominant inflammatory response to stretch in the early VO in the ACF rat, suggesting an important role of TNF-α in initiating pathophysiological response of myocardium to VO. [Copyright &y& Elsevier]