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Abstract Fully π-conjugated polymers with rigid aromatic units are promising for flexible optoelectronic devices, but their inherent brittleness poses a challenge for achieving high-performance, intrinsically stretchable fully π-conjugated polymer. Here, we are establishing an external-plasticizing strategy using semiconductor fluid plasticizers (Z1 and Z2) to enhance the optoelectronic, morphological, and stretchable properties of fully π-conjugated polymer films for flexible light-emitting diodes. The synergistic effect of hierarchical structure and optoelectronic properties of Z1 in poly(9,9-di-n-octylfluorene-alt-benzothiadiazole) (F8BT) films enable excellent stretchable deformability (~25%) and good conductivity. PLEDs based on F8BT/Z1 films show stable electroluminescence and efficiency under 15% stretch and 100 cycles at 10% strain, revealing outstanding stress tolerance. This strategy is also improving the stretchable properties of polymers like poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) and poly(2-methoxy-5(2′-ethyl)hexoxy-phenylenevinylene) (Super Yellow), demonstrating its general applicability. Therefore, this strategy can provide effective guidance for designing high-performance stretchable fully π-conjugated polymers films for flexible electronic devices.

Local defects in coatings allow aggressive electrolytes penetrate to the coating/substrate interface, accelerating the corrosion of the exposed Mg substrate and compromising its biocompatibility. In this work, self-healing calcium hydrogen phosphate dihydrate (DCPD) coating incorporated with 3,5-dinitrosalicylic acid (3,5-D) or 5-amino salicylic acid (5-A) is designed on Mg. The results reveal that the self-healing and corrosion resistance performance of DCPD improves after adding 3,5-D/5-A. Namely, incorporating 3,5-D/5-A into DCPD accelerates the self-healing process and repair the coating at the initial stage. The released 3,5-D/5-A additives could adsorb on the exposed Mg surface and combine with the Ca2+ ions to precipitate. The interfacial adsorption mechanism of 3,5-D/5-A additives is disclosed by quantum chemical calculation. The simultaneously responsive adsorption and deposition of additives during coating degradation increase the thickness and compactness of the deposition layer at the coating defects, further inhibiting corrosion and stabilizing pH. These findings suggest taking biocompatibility recovery into consideration of preparing self-healing coating for biomedical applications.

Aluminum (Al) and its alloys have been widely used in daily life, but the absence of antibacterial properties makes them potential vectors for bacterial transmission. In this study, an Ag-doped TiO2 coating was successfully prepared on the porous surface of etched Al foil using the sol-gel method. The results indicated that the porous layer allowed the gel to permeate through the holes, thereby forming an interface carrying these antibacterial agents with a thickness of about 10 μm. The Ag dopant promoted the transformation of titania from rutile to anatase during the calcination process, with the rutile being absent when the atomic ratio of Ag to Ti reached 0.10. Meanwhile, the doped Ag+ was thermally decomposed into metallic Ag0. As a result, doping Ag enhanced the photocatalytic efficacy of TiO2 coating. Moreover, the antibacterial rate of this coating against Escherichia coli and Staphylococcus aureus under dark conditions could reach more than 99%, and the corrosion resistance of the Al foil was also slightly improved by it.

Abstract Background Potentially inappropriate medications (PIMs) are common among older adults with cancer, but their association with overall survival (OS) among non-small cell lung cancer (NSCLC) patients remains unclear. This study aimed to investigate the association between the use of PIMs and OS in patients with NSCLC. Methods In this cohort study, we included patients ≥ 65 years with newly diagnosed NSCLC from January 2014 to December 2020. Potentially inappropriate medication (PIM) is defined by the Beers criteria of 2019 at baseline and within six months following the initiation of systemic therapy. Multivariable Cox regression model was built to assess the association between PIMs and overall survival (OS). Results We finally included 338 patients with a median follow-up for OS of 1777 days. The prevalence of patients receiving at least one PIM was 39.9% (135/338) and 61.2% (71/116) at baseline and after systemic therapy, respectively. The most important factor associated with PIM use was the number of prescribed medications (P

Doxorubicin (DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients, but related pharmacotherapeutic measures are relatively limited. Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity. Idebenone, a novel ferroptosis inhibitor, is a well-described clinical drug widely used. However, its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear. In this study, we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism. A single intraperitoneal injection of DOX (15 mg/kg) was administrated to establish DOX-induced cardiotoxicity. The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe2+ and ROS overload, which resulted in ferroptosis. CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1. Interestingly, idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX. Idebenone could form stable hydrogen bonds with FSP1 protein at K355, which may influence its association with ubiquitin. The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation. In conclusion, this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1, making it a potential clinical drug for patients receiving DOX treatment.

From the standpoint of chemical structures, the organic backbones of energetic materials can be classified into aromatic rings, nonaromatic rings, and open chains. Although the category of aromatic energetic compounds exhibits several advantages in the regulation of energetic properties, the nonaromatic heterocycles, assembling nitramino explosophores with simple alkyl bridges, still have prevailed in benchmark materials. The methylene bridge plays a pivotal role in the constructions of the classic nonaromatic heterocycle-based energetic compounds, e.g., hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), whereas ethylene bridge is the core moiety of state-of-the-art explosive 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). In this context, it is of great interest to employ simple and practical bridges to assemble aromatic and nonaromatic nitrogen-rich heterocycles, thereby expanding the structural diversity of energetic materials, e.g., bridged and fused nitrogen-rich poly-heterocycles. Furthermore, alkyl-bridged poly-heterocycles highlight the potential for the open chain type of energetic materials. In this review, the development of alkyl bridges in linking nitrogen-rich heterocycles is presented, and the perspective of the newly constructed energetic backbones is summarized for the future design of advanced energetic materials.

Abstract Biosynthesis of paclitaxel (Taxol™) is a hot topic with extensive and durable interests for decades. However, it is severely hindered due to the very low titers of intermediates. In this study, Escherichia coli was employed to de novo synthesize a key intermediate of paclitaxel, taxadien-5α-yl-acetate (T5OAc). Plasmid-based pathway reconstruction and optimization were conducted for T5OAc production. The endogenous methylerythritol phosphate pathway was enhanced to increase the precursor supply. Three taxadien-5α-ol O-acetyltransferases were tested to obtain the best enzyme for the acetylation step. Metabolic burden was relieved to restore cell growth and promote production through optimizing the plasmid production system. In order to achieve metabolic balance, the biosynthesis pathway was regulated precisely by multivariate-modular metabolic engineering. Finally, in a 5-L bioreactor, the T5OAc titer was enhanced to reach 10.9 mg/L. This represents an approximately 272-fold increase in production compared to the original strain, marking the highest yield of T5OAc ever documented in E. coli, which is believed to be helpful for promoting the progress of paclitaxel biosynthesis.

Abstract Temporal regulation of super-enhancer (SE) driven transcription factors (TFs) underlies normal developmental programs. Neuroblastoma (NB) arises from an inability of sympathoadrenal progenitors to exit a self-renewal program and terminally differentiate. To identify SEs driving TF regulators, we use all-trans retinoic acid (ATRA) to induce NB growth arrest and differentiation. Time-course H3K27ac ChIP-seq and RNA-seq reveal ATRA coordinated SE waves. SEs that decrease with ATRA link to stem cell development (MYCN, GATA3, SOX11). CRISPR-Cas9 and siRNA verify SOX11 dependency, in vitro and in vivo. Silencing the SOX11 SE using dCAS9-KRAB decreases SOX11 mRNA and inhibits cell growth. Other TFs activate in sequential waves at 2, 4 and 8 days of ATRA treatment that regulate neural development (GATA2 and SOX4). Silencing the gained SOX4 SE using dCAS9-KRAB decreases SOX4 expression and attenuates ATRA-induced differentiation genes. Our study identifies oncogenic lineage drivers of NB self-renewal and TFs critical for implementing a differentiation program.

Abstract Background Although acetaminophen is widely used in women during pregnancy, its safety has not been clearly stated. The study aimed to investigate the association between acetaminophen use and adverse pregnancy outcomes in pregnant women in China. Methods We conducted a retrospective cohort study by collecting data on pregnant women who delivered in the Beijing Obstetrics and Gynecology Hospital from January 2018 to September 2023. An acetaminophen use group and a control group were formed based on prenatal exposure to acetaminophen. The pregnancy outcomes that we focused on were stillbirth, miscarriage, preterm birth, APGAR score, birth weight, and congenital disabilities. Pregnant women exposed to acetaminophen were matched to unexposed in a 1:1 ratio with propensity score matching, using the greedy matching macro. SPSS software was used for statistical analysis. Multivariable logistics regression was used to assess the association between acetaminophen use during pregnancy and adverse pregnancy outcomes. Results A total of 41,440 pregnant women were included, of whom 501 were exposed to acetaminophen during pregnancy, and 40,939 were not exposed. After the propensity score matching, the acetaminophen use and control groups consisted of 501 pregnant women each. The primary analysis showed that acetaminophen exposure during pregnancy was associated with an increased risk of stillbirth (adjusted OR (aOR) = 2.29, 95% CI, 1.19–4.43), APGAR score

Abstract Compressional and shear wave velocities of polycrystalline stishovite (SiO2) have been measured at simultaneous high pressures and temperatures up to 14.5 GPa and 800°C. By fitting velocities to the finite strain equations, the elastic moduli and density were determined to be KS0 = 306.6(46) GPa, KS′ = 4.92(10), ∂KS/∂T = −0.024(1) GPa/K, G0 = 229.0(34) GPa, G′ = 1.07(10), ∂G/∂T = −0.017(1) GPa/K, ρ0 = 4.287(2) g/cm3. Our modeling suggested that, in the eclogite, coesite‐stishovite transition can increase P and S wave velocities by 2.4% and 3.5%, respectively. A comparison between geophysical observations and our model shows that the coesite‐stishovite phase transition in the eclogite can potentially be responsible for the occurrence of the X discontinuity beneath Hawaii. In addition, our current results suggest an eclogite‐rich layer between 340 and 450 km depth beneath Hawaii. The eclogite concentration at the top and bottom of the layer is 41–55 vol% and >77 vol%, respectively.

Although most source apportionments of VOCs use mixing ratios, about 23 % of published studies use mass concentrations. Thus, systematically exploring the changes in VOC source apportioned results caused by metric differences is important to assess the differences in key precursor apportionment results given the observed increases in O3 pollution situation. Different monitoring instruments measured hourly VOC volumetric concentrations in three typical Chinese cities (i.e., Qingdao, Shijiazhuang, and Zhumadian). Converting volumetric to mass concentrations under standard and/or actual temperature–pressure conditions, VOC values with different metrics were obtained. The impacts of different metrics on the source apportionments were then investigated. Compared to the positive matrix factorization of the volumetric data (VC-PMF), the VOC species concentrations with low relative molecular mass (RMM) in the factor profiles substantially decreased in mass data analyses (MC-PMF). However, those species with high RMM substantially increased. There were no substantial differences in the apportioned source contributions based on standard and actual condition mass concentrations. However, the high-low rankings of percent contributions apportioned using the volumetric and mass data produced substantial differences. Compared with the VC-PMF results, the percent contributions of sources dominated by species with low RMM (e.g., natural gas usage and mixed sources containing natural gas usage) apportioned by MC-PMF decreased, while those of sources that emitted high RMM species (e.g., solvent usage and mixed sources containing solvent usage) increased. Source apportionments based on the volumetric concentration data had more practical significance compared to the mass concentration data results for control strategy development since the mass data analyses created issues.

Objectives: Killer cell lectin like receptor G1 (KLRG1) is identified as a co-inhibitory receptor for NK cells and antigen-experienced T cells. The role of KLRG1 in immune regulation in patients with non-small cell lung cancer (NSCLC) remains poorly understood. Materials and Methods: We measured the proportion and immune function of KLRG1+CD8+ T cells derived from peripheral blood in patients with NSCLC by flow cytometry. Besides, using data from the gene expression profiles and single-cell sequencing, we explored the expression and immune role of KLRG1 in tumor tissues of patients with NSCLC. We further determined the prognostic value of KLRG1 in terms of overall survival (OS) in NSCLC patients. Results: We found that the proportion of KLRG1+CD8+T cells in peripheral blood significantly increased in patients with NSCLC as compared to those with benign pulmonary nodules and healthy donors. Peripheral KLRG1+CD8+T cell proportion was increased in elder subjects compared to that in younger ones, implying an immunosenescence phenotype. Moreover, the KLRG1+CD8+T cell levels were positively correlated with tumor size and TNM stage in the NSCLC cohort. In vitro stimulation experiments demonstrated that the KLRG1+CD8+T cells from peripheral blood expressed higher levels of Granzyme B and perforin than the KLRG1−CD8+ T cells. However, single-cell RNA sequencing data revealed that the KLRG1+CD8+ T cells were less infiltrated in tumor microenvironment and exhibited impaired cytotoxicity. The KLRG1 gene expression levels were significantly lower in tumor tissues than that in normal lung tissues, and were inversely correlated with CDH1 expression levels. Moreover, higher expression of CDH1 in tumor tissues predicted worse overall survival only in patients with KLRG1-high expression, but not in the KLRG1-low subset. Conclusion: This study demonstrates that KLRG1+CD8+T cells were associated with tumor immune evasion in NSCLC and suggests KLRG1 as a potential immunotherapy target.

In this paper, we consider the radially symmetric spacelike solutions of a nonlinear Dirichlet problem for the prescribed mean curvature spacelike equation in a Friedmann–Lemaître–Robertson–Walker spacetime. By using a conformal change of variable, this problem can be translated an equivalent problem in the Minkowski spacetime. By using the lower and upper solution method, fixed point, a priori bounds and topological degree method, we obtain the existence, nonexistence and multiplicity of radially symmetric spacelike solutions.

Stenotrophomonas maltophilia (S. maltophilia) is an emerging opportunistic pathogen that exhibits resistant to a majority of commonly used antibiotics. Phages have the potential to serve as an alternative treatment for S. maltophilia infections. In this study, a lytic phage, A1432, infecting S. maltophilia YCR3A-1, was isolated and characterized from a karst cave. Transmission electron microscopy revealed that phage A1432 possesses an icosahedral head and a shorter tail. Phage A1432 demonstrated a narrow host range, with an optimal multiplicity of infection of 0.1. The one-step growth curve indicated a latent time of 10 min, a lysis period of 90 min, a burst size of 43.2 plaque-forming units per cell. In vitro bacteriolytic activity test showed that phage A1432 was capable to inhibit the growth of S. maltophilia YCR3A-1 in an MOI-dependent manner after 2 h of co-culture. BLASTn analysis showed that phage A1432 genome shares the highest similarity (81.46%) with Xanthomonas phage Xoo-sp2 in the NCBI database, while the query coverage was only 37%. The phage contains double-stranded DNA with a genome length of 61,660 bp and a GC content of 61.92%. It is predicted to have 79 open reading frames and one tRNA, with no virulence or antibiotic resistance genes. Phylogenetic analysis using terminase large subunit and DNA polymerase indicated that phage A1432 clustered with members of the Bradleyvirinae subfamily but diverged into a distinct branch. Further phylogenetic comparison analysis using Average Nucleotide Identity, proteomic phylogenetic analysis, genomic network analysis confirmed that phage A1432 belongs to a novel genus within the Bradleyvirinae subfamily, Mesyanzhinovviridae family. Additionally, phylogenetic analysis of the so far isolated S. maltophilia phages revealed significant genetic diversity among these phages. The results of this research will contribute valuable information for further studies on their morphological and genetic diversity, will aid in elucidating the evolutionary mechanisms that give rise to them.

Silicon carbide ceramic membranes are known as a new generation of membrane products due to their excellent chemical stability and high flux advantages. This article, based on the PatSnap patent analysis, analyzes the global patents of silicon carbide ceramic membranes, preparation methods, devices and equipment, application-related patents, and applicants from perspectives of patent applications, patent layouts, and international patent classification technical categories. It concludes that the technological hotspots in the field of silicon carbide ceramic membranes are concentrated on improving separation efficiency through separation applications, providing a reference for the technical improvement, application, and patent layout of silicon carbide ceramic membranes.

Background: Azvudine was approved for the treatment of coronavirus disease 2019 (COVID-19) in China and has been widely used since the outbreak in December 2022. However, real-world research on the adherence of Azvudine is lacking. Additionally, limited research exists on determining the optimal duration for Azvudine treatment. Methods: We studied adult patients with COVID-19 who got Azvudine or supportive treatment at an outpatient department between December 19, 2022 and January 5, 2023. The enrolled patients were divided into two groups: the Azvudine group, which received Azvudine, and the control group, which only received supportive care. We recorded their information and analyzed it using descriptive statistics. The primary outcome of this study was the compliance of outpatients with Azvudine, and the secondary outcome of this study was the optimal duration of Azvudine. Inverse probability weighting (IPW) was used to address the imbalance between groups when comparing the optimal duration of Azvudine, and Cox regression to evaluate the effect of Azvudine on the 28-day disease progression rate. Results: We enrolled a total of 882 patients, of which 382 received Azvudine. Among the patients, 94.0 % (359) had good compliance, and non-compliance was primarily attributed to dosage errors. Azvudine appeared to have a beneficial therapeutic effect when administered for at least 7 days. Conclusions: Outpatients have relatively good compliance with Azvudine, and optimal therapeutic effects were observed with the recommended duration of at least 7 days.

Diabetic cardiomyopathy (DCM) is a common severe complication of diabetes that occurs independently of hypertension, coronary artery disease, and valvular cardiomyopathy, eventually leading to heart failure. Previous studies have reported that Tectorigenin (TEC) possesses extensive anti-inflammatory and anti-oxidative stress properties. In this present study, the impact of TEC on diabetic cardiomyopathy was examined. The model of DCM in mice was established with the combination of a high-fat diet and STZ treatment. Remarkably, TEC treatment significantly attenuated cardiac fibrosis and improved cardiac dysfunction. Concurrently, TEC was also found to mitigate hyperglycemia and hyperlipidemia in the DCM mouse. At the molecular level, TEC is involved in the activation of AMPK, both in vitro and in vivo, by enhancing its phosphorylation. This is achieved through the regulation of endothelial-mesenchymal transition via the AMPK/TGFβ/Smad3 pathway. Furthermore, it was demonstrated that the level of ubiquitination of the adiponectin receptor 1 (AdipoR1) protein is associated with TEC-mediated improvement of cardiac dysfunction in DCM mice. Notably the substantial reduction of myocardial fibrosis. In conclusion, TEC improves cardiac fibrosis in DCM mice by modulating the AdipoR1/AMPK signaling pathway. These findings suggest that TEC could be an effective therapeutic agent for the treatment of diabetic cardiomyopathy.

Among the bioactive compounds, lipid-soluble tanshinone is present in Salvia miltiorrhiza, a medicinal plant species. While it is known that ethephon has the ability to inhibit the tanshinones biosynthesis in the S. miltiorrhiza hairy root, however the underlying regulatory mechanism remains obscure. In this study, using the transcriptome dataset of the S. miltiorrhiza hairy root induced by ethephon, an ethylene-responsive transcriptional factor EIN3-like 1 (SmEIL1) was identified. The SmEIL1 protein was found to be localized in the nuclei, and confirmed by the transient transformation observed in tobacco leaves. The overexpression of SmEIL1 was able to inhibit the tanshinones accumulation to a large degree, as well as down-regulate tanshinones biosynthetic genes including SmGGPPS1, SmHMGR1, SmHMGS1, SmCPS1, SmKSL1 and SmCYP76AH1. These are well recognized participants in the tanshinones biosynthesis pathway. Further investigation on the SmEIL1 was observed to inhibit the transcription of the CPS1 gene by the Dual-Luciferase (Dual-LUC) and yeast one-hybrid (Y1H) assays. The data in this work will be of value regarding the involvement of EILs in regulating the biosynthesis of tanshinones and lay the foundation for the metabolic engineering of bioactive ingredients in S. miltiorrhiza.

Abstract Prophages, which enables bacterial hosts to acquire novel traits, and increase genetic variation and evolutionary innovation, are considered to be one of the greatest drivers of bacterial diversity and evolution. Stenotrophomonas maltophilia is widely distributed and one of the most important multidrug resistant bacteria in hospitals. However, the distribution and genetic diversity of S. maltophilia prophages have not been elucidated. In this study, putative prophages were predicted in S. maltophilia genomes by using virus prediction tools, and the genetic diversity and phylogeny of S. maltophilia and the prophages they harbor were further analyzed. A total of 356 prophage regions were predicted from 88 S. maltophilia genomes. Among them, 144 were intact prophages, but 77.09% of the intact prophages did not match any known phage sequences in the public database. The number of prophage carried by S. maltophilia is related to its host habitat and is an important factor affecting the size of the host genome, but it is not related to the genetic diversity of the prophage. The prediction of auxiliary genes encoded by prophage showed that antibiotic resistance genes was not predicted for any of the prophages except for one questionable prophage, while 53 virulence genes and 169 carbohydrate active enzymes were predicted from 11.24 and 44.1% prophages, respectively. Most of the prophages (72.29%) mediated horizontal gene transfer of S. maltophilia genome, but only involved in 6.25% of the horizontal gene transfer events. In addition, CRISPR prediction indicated 97.75% S. maltophilia strains contained the CRISPR-Cas system containing 818 spacer sequences. However, these spacer sequences did not match any known S. maltophilia phages, and only a few S. maltophilia prophages. Comparative genomic analysis revealed a highly conserved and syntenic organization with genomic rearrangement between the prophages and the known related S. maltophilia phages. Our results indicate a high prevalence and genetic diversity of prophages in the genome of S. maltophilia, as well as the presence of a large number of uncharacterized phages. It provides an important complement to understanding the diversity and biological characteristics of phages, as well as the interactions and evolution between bacteria and phages.

Abstract Introduction Diet selection of grazing livestock is one of the critical factors affecting the diversity and composition of plant communities in grasslands, with consequent impacts for ecosystem functioning. Co‐grazing of multiple livestock species could create additive or complementary effects on plant communities due to diet overlap or differentiation among livestock species. However, there is only limited knowledge about diet overlap and differentiation of co‐occurring livestock species and whether or how these diet characteristics change with grassland degradation. Materials and Methods We experimentally test the diets of two commonly co‐occurring livestock species (cattle and sheep) and the dietary niche partitioning/overlap between them in non‐degraded, moderately and severely degraded grasslands. Results Cattle exhibited broader diet than sheep, and diet overlap between species was lower in non‐degraded grasslands. As grassland degradation increased the availability of annual plants, interspecific niche overlap between cattle and sheep gradually increased, and cattle suffered a resulting dietary niche compression. Sheep maintained a relatively narrow and constant dietary breadth. Conclusion The increasing dietary niche overlap between livestock species with increasing extent of grassland degradation indicated increased additive effects of cattle and sheep co‐grazing on plant community, and thus stronger effects on plant community composition and diversity.

MYCN activates canonical MYC targets involved in ribosome biogenesis, protein synthesis, and represses neuronal differentiation genes to drive oncogenesis in neuroblastoma (NB). How MYCN orchestrates global gene expression remains incompletely understood. Our study finds that MYCN binds promoters to up-regulate canonical MYC targets but binds to both enhancers and promoters to repress differentiation genes. MYCN binding also increases H3K4me3 and H3K27ac on canonical MYC target promoters and decreases H3K27ac on neuronal differentiation gene enhancers and promoters. WDR5 facilitates MYCN promoter binding to activate canonical MYC target genes, whereas MYCN recruits G9a to enhancers to repress neuronal differentiation genes. Targeting both MYCN's active and repressive transcriptional activities using both WDR5 and G9a inhibitors synergistically suppresses NB growth. We demonstrate that MYCN cooperates with WDR5 and G9a to orchestrate global gene transcription. The targeting of both these cofactors is a novel therapeutic strategy to indirectly target the oncogenic activity of MYCN.

Background: In the process of international communication in Chinese Wushu (ICCW), the government controls the orientation, scale, pace. However, the ICCW currently lacks a standardised government capacity structural system, and a detailed study of framework construction may be required to ensure the smooth development of the ICCW.Objectives: This study aims to clarify these elements and construct a framework for a governmental capacity system for ICCW.Methods: For this purpose, an expert interview outline was designed, and in-depth interviews were conducted with 61 experts. Using grounded theory in the qualitative research method, NVivo 12 software was used to conduct a three-level coding analysis of the interview text for data processing and analysis.Results: We extracted 58 opening codes and 11 tree nodes and categorised them into three core categories: supply side government capacity, environment-side government capacity, and demand-side government capacity, accounting for 62.36 %, 24.76 %, and 12.86 % of the total, respectively, which jointly constructed the framework structure system of the governmental capacity system for the ICCW.Conclusions: This study found that these three-dimensional government capacities have synergistic effects and that multiple measures work together. The government should ensure the supply side's direct promotion effect; the environmental side's indirect influencing effect; and the demand side's internal driving effect to promote ICCW. Meanwhile, a closed-loop systematic study of communication processes should be conducted in combination with communication organisations and individuals.

Background and aimsAmnestic mild cognitive impairment (aMCI) is the most common subtype of MCI, which carries a significantly high risk of transitioning to Alzheimer’s disease. Recently, increasing attention has been given to remnant cholesterol (RC), a non-traditional and previously overlooked risk factor. The aim of this study was to explore the association between plasma RC levels and aMCI.MethodsData were obtained from Brain Health Cognitive Management Team in Wuhan (https://hbtcm.66nao.com/admin/). A total of 1,007 community-dwelling elders were recruited for this project. Based on ten tools including general demographic data, cognitive screening and some exclusion scales, these participants were divided into the aMCI (n = 401) and normal cognitive groups (n = 606). Physical examinations were conducted on all participants, with clinical indicators such as blood pressure, blood sugar, and blood lipids collected.ResultsThe aMCI group had significantly higher RC levels compared to the normal cognitive group (0.64 ± 0.431 vs. 0.52 ± 0.447 mmol/L, p

Abstract Background Peritonitis is the most important complication of peritoneal dialysis (PD) and coagulase-negative staphylococci (CNS) are a frequent cause of dialysis-related infections. The association between SCCmec typing with psm-mec positivity in staphylococci and PD-related infections has not been identified. We aim to investigate the molecular epidemiology of CNS isolated from PD-peritonitis in a single Chinese center, focusing on the genetic determinants conferring methicillin resistance. Methods We collected 10 genetically unrelated CNS isolates from 10 patients with CNS PD-related peritonitis. The patients were divided into two groups based on the results of MIC to oxacillin: the methicillin-resistant CNS (MRCNS) and methicillin-sensitive CNS (MSCNS) groups. The biofilm formation group (BFG) and the non-biofilm formation group (NBFG) were used as the control groups. Phenotypic and molecular methods were used to analyze SCCmec types I, II and III, associated genes and biofilm formation and the existence of psm-mec. The demographic data and clinical indicators were collected. Results Ten CNS PD-related peritonitis patients were enrolled for this study. There were 6 MRCNS and 4 MRCNS isolates. SCCmec types were fully determined in 10 isolates. Seven staphylococci (70%) carried SCCmec, of which 4 isolates carried single SCCmec type I (40%) and 3 isolates had multiple SCCmec elements (I + III). Of the 6 MRCNS isolates, 3 carried SCCmec type I (50%) and 2 isolates carried SCCmec type I + III (33.3%). A high diversity of ccr types, mec complexes and ccr-mec complex combinations was identified among the 10 CNS isolates. The psm-mec gene was detected in 2/10 (20%) CNS isolates. There was no mutation in the psm-mec gene. Conclusions The majority of isolates were hospital-associated isolates. Furthermore, 2 psm-mec positive isolates were MRCNS in the NBFG. The PD patients frequent exposure to hospital would be the main risk factor. The presence of the psm-mec signal in the spectra of the MRCNS tested here demonstrates the presence of certain SCCmec cassettes that convey methicillin resistance.

The self-centering buckling-restrained brace (SC-BRB) may achieve self-restoration for structures and, to a certain degree, diminish the substantial seismic residual deformation following rare earthquakes when compared to the usage of the conventional buckling-restrained brace (BRB). It may be possible to reduce the abrupt change in stiffness at the location of the strengthened stories and make the outrigger better at dissipating energy by improving the design of the energy-dissipation outrigger. This study compares the seismic performances of two types of energy-dissipation outriggers with BRB and SC-BRB web member designs during rare earthquakes so that the changes can be measured. The results show that using the SC-BRB web member design reduces the maximum inter-story drift ratio by an average of 7.68% and increases the average plastic-energy dissipation of the outrigger truss by 8.75%. The evaluation results showthat the SC-BRB outrigger truss structure has better structural regularity and energy-dissipation performance. It has the ability to efficiently regulate the structural seismic response and lessen primary-structure damage.

Abstract Background Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection. Methods A panel of 53 tumor cell lines of different origins was used. The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Finally, in vivo experiments were performed by implanting cultured cells or fragments of tumors into immunodeficient mice. Results Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. SAC abrogation induced activation of CASP-2, leading to cleavage of CASP-3 and extensive cell death only in presence of high levels of BID. Finally, a prevalence study revealed high BID mRNA in 6% of human solid tumors. Conclusions The fate of tumor cells after SAC abrogation is driven by an AURKB/ CASP-2 signaling mechanism, regulated by BID levels. Our results pave the way to clinically explore SAC-targeting drugs in tumors with high BID expression.

Highlights Trace amounts of long-chain gemini surfactants are essential for blade-coating of high-quality perovskite films, enabling a 17.05% efficient full printed carbon-based module (50 cm2 active area). Only when the surfactant chain is over a critical length will the gemini surfactant be effective for blade-coating of perovskite films. The surfactants increase the capillary number of perovskite precursor solution, reduce the local disturbance and combat inhomogeneous solidification during blade coating, thus allowing high-quality perovskite films to be formed.

Traditional automatic gardening pruning robots generally employ electronic fences for the delineation of working boundaries. In order to quickly determine the working area of a robot, we combined an improved DeepLabv3+ semantic segmentation model with a simultaneous localization and mapping (SLAM) system to construct a three-dimensional (3D) semantic map. To reduce the computational cost of its future deployment in resource-constrained mobile robots, we replaced the backbone network of DeepLabv3+, ResNet50, with MobileNetV2 to decrease the number of network parameters and improve recognition speed. In addition, we introduced an efficient channel attention network attention mechanism to enhance the accuracy of the neural network, forming an improved Multiclass MobileNetV2 ECA DeepLabv3+ (MM-ED) network model. Through the integration of this model with the SLAM system, the entire framework was able to generate a 3D semantic point cloud map of a lawn working area and convert it into octree and occupancy grid maps, providing technical support for future autonomous robot operation and navigation. We created a lawn dataset containing 7500 images, using our own annotated images as ground truth. This dataset was employed for experimental purposes. Experimental results showed that the proposed MM-ED network model achieved 91.07% and 94.71% for MIoU and MPA metrics, respectively. Using a GTX 3060 Laptop GPU, the frames per second rate reached 27.69, demonstrating superior recognition performance compared to similar semantic segmentation architectures and better adaptation to SLAM systems.

Taxadiene is an important precursor for the biosynthesis of highly effective anticancer drug paclitaxel, but its microbial biosynthesis yield is very low. In this study, we employed Yarrowia lipolytica as a microbial host to produce taxadiene. First, a “push–pull” strategy was adopted to increase taxadiene production by 234%. Then taxadiene synthase was fused with five solubilizing tags respectively, leading a maximum increase of 62.3% in taxadiene production when fused with SUMO. Subsequently, a multi-copy iterative integration method was used to further increase taxadiene titer, achieving the maximum titer of 23.7 mg/L in shake flask culture after three rounds of integration. Finally, the taxadiene titer was increased to 101.4 mg/L by optimization of the fed-batch fermentation conditions. This is the first report of taxadiene biosynthesis accomplished in Y. lipolytica, serving as a good example for the sustainable production of taxadiene and other terpenoids in this oleaginous yeast.

Abstract Knowledge Graphs (KGs) describe objective facts in the form of RDF triples, each triple contains sufficient semantic information and triple structure information. Knowledge Graph Completion (KGC) is to acquire new knowledge by predicting hidden relationships between entities and adding the new knowledge to the KG. At present, the mainstream KGC approaches only applied the triple structure information or only utilized the semantic information of the text. This paper proposes an approach (TSTR) using BERT and deep neural networks to fully extract the semantic information of knowledge, and designs an aggregated re-ranking scheme that incorporates existing graph embedding approach to learn the structural information of triples. In experiments, the approach achieves state-of-the-art performance on three benchmark datasets, and outperforms recent KGC approaches on sparsely connected datasets.

Developing a highly efficient water-splitting photocatalyst for hydrogen production under visible light is urgent. In this study, β-SiC nanowire photocatalysts loaded with 0.01–0.1 wt. % nickel were prepared. Their microstructure and hydrogen production activity were studied. The catalyst with 0.05 wt. % nickel and a sacrificial agent Na2S–Na2SO3 shows the highest hydrogen production rate of 375.4 µmol g−1 h−1 since the loaded nickel prohibits the recombination of photogenerated electron–hole pairs in the system, which enhances the photocatalytic activity.

In this paper, 75 concrete prisms were tested under different temperatures (20, 200, 400, 600 and 800 °C) and molybdenum tailings replacement ratio (0, 25, 50, 75, and 100 %). The axial compression failure modes and mechanical properties of molybdenum tailings concrete were studied. The results show that the increase in temperature will aggravate the failure of concrete under axial compression, instead of molybdenum tailing replacement ratio. With the increase of temperature (20–800 °C), the surface color of the concrete becomes lighter, and obvious cracks began to appear from 400 °C, the mass loss ratio and peak strain of molybdenum tailings concrete show an increasing trend, and reach the maximum growth ratio (6.58 % and 34 %) at 800 °C. The peak stress and elastic modulus of molybdenum tailings concrete show a decreasing trend, and reach the maximum reduction at 800 °C (52 % and 71 %). With the increase of replacement ratio, the mass loss ratio of molybdenum tailings concrete increases linearly. The peak stress, peak strain and elastic modulus of molybdenum tailings concrete at all temperatures increase first and then decrease. The 25 % molybdenum tailings content can improve the deterioration of molybdenum tailings concrete after exposure to high temperature. Based on the experimental data, the prediction formulas of peak stress/strain and elastic modulus of molybdenum tailings under different temperature-molybdenum tailings replacement ratio coupling conditions are fitted respectively. The experimental and calculated values of the formula are in good agreement.

Background and aimsEstimated pulse wave velocity (ePWV) and systemic inflammatory response index (SIRI) have been recently investigated as a marker of arterial stiffness and a novel systemic inflammatory indicator. This study aims to examine the independent and combined association of ePWV and SIRI with incident stroke and its subtypes.MethodsData of the Dongfeng-Tongji cohort study was analyzed for 9,154 middle-aged and older adults, who were free of cardiovascular disease and cancer and were followed up to document incident stroke. But their association with incident stroke events and its subtypes have not been well studied. Multivariable adjusted Cox regression models were used to determine the independent and combined association of ePWV and SIRI with incident stroke events.ResultsOver a 7.22-year follow-up, the cohort documented 491 stroke cases (387 ischemic stroke and 104 hemorrhagic stroke). The multivariate adjusted model showed that with each one-unit increase in the level of ePWV, the corresponding hazard ratios (HRs) (95% CI) for total stroke, ischemic stroke, and hemorrhagic stroke were 1.53 (95% CI, 1.23–1.90), 1.42 (95% CI, 1.11–1.83), and 1.92 (95% CI, 1.21–3.03), respectively. Similarly, with each one-unit increase in log-transformed levels of SIRI, the corresponding HRs (95% CI) for total stroke, ischemic stroke, and hemorrhagic stroke were 1.23 (95% CI,1.04–1.47), 1.16 (95% CI, 0.96–1.41), and 1.52 (95% CI, 1.05–2.20), respectively. There appeared to be a combined effect of ePWV and SIRI on stroke; Participants with high levels of both ePWV and SIRI had a higher risk of total stroke and hemorrhagic stroke, with multiple adjusted HR of 2.43 (95% CI, 1.09–5.42). Additionally, the incorporation of ePWV in addition to traditional cardiovascular risk factors significantly improved the predictive accuracy for total stroke with C statistic increased from 0.684 (95% CI, 0.661–0.707) to 0.687 (95% CI, 0.664–0.710; x2 = 6.65; p for difference = 0.010), and (suggestively) for ischemic stroke with C statistic increased from 0.684 (95% CI, 0.659–0.71) to 0.691(95% CI, 0.666–0.717; x2 = 3.13, p for difference = 0.077), respectively.ConclusionsThe presence of both high ePWV and SIRI individually, as well as together, was found to be associated with an increased incidence of stroke. The combined stroke risk assessment using these two indicators could potentially improve non-invasive assessment and treatment strategies for high-risk patients, as these indicators are easily accessible in clinical practice.

The Al–Cr–Mo–Ni system is of technical interest because it is an essential system for the thermodynamic modeling of systems related to the Ni- and NiAl-based superalloys. The knowledge of phase behaviors and thermodynamic properties of this system will be greatly helpful for the development of related alloys. Thermodynamic modeling of the Al–Cr–Mo–Ni system in the previous effort is not satisfactory. In this study, the Cr–Mo–Ni system was re-optimized with more sophisticated binary databases, and a new thermodynamic database of the Al–Cr–Mo–Ni system was established. A satisfactory agreement between calculated results and experimental data was obtained. The thermodynamic database developed in this study is suitable for assisting the design of both Ni- and NiAl-based superalloys.

BackgroundWhether keratoconus (KC) is an inflammatory disease is currently debated. Hence, we aimed to investigate the immune-related features of KC based on single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data.MethodsscRNA-seq data were obtained from the Genome Sequence Archive (GSA), bulk RNA-seq data were obtained from the Gene Expression Omnibus (GEO), and immune-associated genes(IAGs) were obtained from the ImmPort database. Cell clusters of KC were annotated, and different cell clusters were then selected. The IAG score of each cell was calculated using the AUCell package. Three bulk RNA-seq datasets were merged and used to identify the differentially expressed genes (DEGs), biological functions, and immune characteristics. Weighted gene coexpression network analysis (WGCNA) was used to select the IAG score-related hub genes. Based on scRNA-seq and bulk RNA-seq analyses, three machine learning algorithms, including random forest (RF), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) regression analysis, were used to identify potential prognostic markers for KC. A predictive nomogram was developed based on prognostic markers.ResultsSix cell clusters were identified in KC, and decreased corneal stromal cell-5 (CSC-5) and increased CSC-6 were found in KC. CSC and immune cell clusters had the highest IAG scores. The bulk RNA-seq analysis identified 1362 DEGs (553 upregulated and 809 downregulated) in KC. We found different immune cell populations and differentially expressed cytokines in KC. More than three key IAG score-related modules and 367 genes were identified. By integrating the scRNA-seq and bulk RNA-seq analyses, 250 IAGs were selected and then incorporated into three machine learning models, and 10 IAGs (CEP112, FYN, IFITM1, IGFBP5, LPIN2, MAP1B, RNASE1, RUNX3, SMIM10, and SRGN) were identified as potential prognostic genes that were significantly associated with cytokine and matrix metalloproteinase(MMP)1-14 expression. Finally, a predictive nomogram was constructed and validated.ConclusionTaken together, our results identified CSCs and immune cell clusters that may play a key role during KC progression by regulating immunological features and maintaining cell stability.

In this paper, we show the positive solutions set for one-dimensional $ p $-Laplacian problem with sign-changing weight contains a reversed $ S $-shaped continuum. By figuring the shape of unbounded continuum of positive solutions, we identify the interval of bifurcation parameter in which the $ p $-Laplacian problem has one or two or three positive solutions according to the asymptotic behavior of nonlinear term at 0 and $ \infty $. The proof of the main result is based upon bifurcation technique.

Abstract The deprotonation mechanism for the phenolic hydroxyl and the complexing of metal ions with a commonly used food additive, propyl gallate (PG) were studied theoretically and experimentally. The interaction of procyanidins [PC, epicatechin16 (4 → 8) catechin], and its basic monomeric unit catechin (CA) with metal ions was studied by the fluorescence quenching spectra. The results showed that the 9-OH quinoid PG was formed at higher pH (10.9) by the oxidization of phenolic hydroxyl. The binding affinities (K a) and stoichiometry of these metal ions with PG were determined. The Al3+ in PG-Al complex [Al(PG)(H2O)2Cl2]- was coordinated at the 8,9-OH doubly deprotonated catechol site with double chloride ions (Cl-) and double water molecules (H2O). The fluorescence quenching titration with Sn2+, Zn2+, Cu2+, Al3+ and Fe3+ revealed that the stoichiometries of metal-bound PC were 1:1, 2:3, 2:3, 2:3 and 1:1, respectively. The presence of bovine serum albumin (BSA) could enhance the complexing strength of PC with metal ions.

The supramolecular coordination doping/blending allow for intermolecular Förster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) in doping/blending films, endowing films with tunable bandgap, high PLQY and high conductivity.

The valve-controlled cylinder drive system is the most common type among hydraulic applications. Nonlinear behaviour in such systems is inevitable when the valve spool is around its null position. We utilised the component linking method to investigate the nonlinearities in a Moog valve-controlled asymmetric cylinder drive system by simulation in Fortran, in which a generalised concept is introduced and validated by comparing to the experimental results. An X factor is proposed in the generalised concept to describe the asymmetric cylinder state, which is a constant when the cylinder is extending or retracting, but numerically calculated when the valve spool is in the underlap region. This analytical solution is approximately 200 times more computationally efficient than the numerical solution method. This paper utilises the component linking method to simulate the Moog valve-controlled asymmetric cylinder drive system in Matlab Simulink, and proposes an analytical solution for the X factor when the valve spool is in the underlap region. This analytical solution is approximately 200 times more computationally efficient than the numerical solution method.

Simultaneous Localization and Mapping (SLAM), as one of the core technologies in intelligent robotics, has gained substantial attention in recent years. Addressing the limitations of SLAM systems in dynamic environments, this research proposes a system specifically designed for plant factory transportation environments, named GY-SLAM. GY-SLAM incorporates a lightweight target detection network, GY, based on YOLOv5, which utilizes GhostNet as the backbone network. This integration is further enhanced with CoordConv coordinate convolution, CARAFE up-sampling operators, and the SE attention mechanism, leading to simultaneous improvements in detection accuracy and model complexity reduction. While mAP@0.5 increased by 0.514% to 95.364, the model simultaneously reduced the number of parameters by 43.976%, computational cost by 46.488%, and model size by 41.752%. Additionally, the system constructs pure static octree maps and grid maps. Tests conducted on the TUM dataset and a proprietary dataset demonstrate that GY-SLAM significantly outperforms ORB-SLAM3 in dynamic scenarios in terms of system localization accuracy and robustness. It shows a remarkable 92.59% improvement in RMSE for Absolute Trajectory Error (ATE), along with a 93.11% improvement in RMSE for the translational drift of Relative Pose Error (RPE) and a 92.89% improvement in RMSE for the rotational drift of RPE. Compared to YOLOv5s, the GY model brings a 41.5944% improvement in detection speed and a 17.7975% increase in SLAM operation speed to the system, indicating strong competitiveness and real-time capabilities. These results validate the effectiveness of GY-SLAM in dynamic environments and provide substantial support for the automation of logistics tasks by robots in specific contexts.

There has been a significant shift in research focus in recent years toward laser-induced graphene (LIG), which is a high-performance material with immense potential for use in energy storage, ultrahydrophobic water applications, and electronic devices. In particular, LIG has demonstrated considerable potential in the field of high-precision human motion posture capture using flexible sensing materials. In this study, we investigated the surface morphology evolution and performance of LIG formed by varying the laser energy accumulation times. Further, to capture human motion posture, we evaluated the performance of highly accurate flexible wearable sensors based on LIG. The experimental results showed that the sensors prepared using LIG exhibited exceptional flexibility and mechanical performance when the laser energy accumulation was optimized three times. They exhibited remarkable attributes, such as high sensitivity (~41.4), a low detection limit (0.05%), a rapid time response (response time of ~150 ms; relaxation time of ~100 ms), and excellent response stability even after 2000 s at a strain of 1.0% or 8.0%. These findings unequivocally show that flexible wearable sensors based on LIG have significant potential for capturing human motion posture, wrist pulse rates, and eye blinking patterns. Moreover, the sensors can capture various physiological signals for pilots to provide real-time capturing.

To study the effects of the jacking stress level, height and strength ratio of the prestress tendons (λ) on the seismic performance of unbonded prestressed concrete (UPC) beams, six UPC beams and one reinforced concrete (RC) beam were tested under cyclic loads. The hysteretic characteristics, skeleton curves, ductility properties, energy dissipation capacity, strain distribution of reinforcement and self-centering capability of the specimens were studied and discussed. Numerical parameter analysis was also carried out by using OpenSees. The results indicate that three failure modes of UPC beams under cyclic loading were observed, namely the tension-failure mode involving a broken rebar, the compression-failure mode involving concrete crushing and the balanced failure. By considering the influence of the prestress position and magnitude, the modified reinforcing index ω was proposed to determine the failure mode. The ω is suggested to be less than 0.3 to ensure sufficient ductility. The effective stress level is linearly and positively related to the stiffness from cracking to yield Kcr and the ultimate bearing capacity of the UPC beam under cyclic loading. The stiffness of the UPC beam is slightly larger than that of the RC beam before yielding, and significantly greater than that of the RC beam after yielding. Due to the large strength reserve after yielding, the integrated seismic performance of the UPC beam is similar to that of the RC beam. When the λ was unchanged, the increase in the relative height of the prestressed tendons αh is beneficial for the overall performance factor F, ductility and crack control. The stiffness degradation performance depends on the λ but is independent of the αh. The total energy dissipation of the non-tensioned UPC specimen was 59% higher than that of the RC beam. The cumulative total energy dissipation of the tensioned UPC specimen was only 13% lower than that of the RC beam with the same number of cycles, indicating that the UPC specimen had a considerable energy dissipation capacity.

Abstract Introduction Sleep abnormalities are highly correlated with neurodevelopmental disorders, such as intellectual disability, attention deficit hyperactivity disorder, and autism spectrum disorders (ASD). The severity of behavioral abnormalities is correlated with the presence of sleep abnormalities. Based on previous research, we investigated that Ctnnd2 gene deletion in mice lead to ASD‐like behaviors and cognitive defects. Given the importance of sleep in individuals with ASD, this study aimed to determine the effects of chronic sleep restriction (SR) on wild‐type (WT) mice and on Ctnnd2 deletion‐induced, neurologically related phenotypes in mice. Method WT and Ctnnd2 knockout (KO) mice were both subjected to manual SR (5 h per day) for 21 consecutively days separately, then we compared neurologically related phenotypes of WT mice, WT mice subjected to SR, KO mice, and KO mice subjected to SR using a three‐chamber assay, direct social interaction test, open‐field test, Morris water maze, Golgi staining, and Western blotting. Results The effects of SR on WT and KO mice were different. After SR, social ability and cognition were impaired in both WT and KO mice. Repetitive behaviors were increased, and exploration abilities were decreased in KO mice but not in WT mice. Moreover, SR reduced the density and area of mushroom‐type dendritic spines in WT rather than KO mice. Finally, the PI3K/Akt‐mTOR pathway was found to be involved in the effects induced by SR‐impaired phenotypes in WT and KO mice. Conclusion Overall, results of the present study may have implications for the role of disrupted sleep in patients with CTNND2 gene‐related autism and the evolution of neurodevelopmental disorders.

Abstract The blast crisis (BC) is the final deadly phase of chronic myeloid leukemia (CML), which remains a major challenge in clinical management. However, the underlying molecular mechanism driving blastic transformation remains unclear. Here, we show that ASF1A, an essential activator, enhanced the transformation to CML-BC by mediating cell differentiation arrest. ASF1A expression was aberrantly increased in bone marrow samples from CML-BC patients compared with newly diagnosed CML-chronic phase (CP) patients. ASF1A inhibited cell differentiation and promoted CML development in vivo. Mechanistically, we identified ASF1A as a coactivator of the Notch transcriptional complex that induces H3K56ac modification in the promoter regions of Notch target genes, and subsequently enhanced RBPJ binding to these promoter regions, thereby enhancing Notch signaling activation to mediate differentiation arrest in CML cells. Thus, our work suggests that targeting ASF1A might represent a promising therapeutic approach and a biomarker to detect disease progression in CML patients.

Abstract The neural crest lineage regulatory transcription factors (TFs) form a core regulatory circuitry (CRC) in neuroblastoma (NB) to specify a noradrenergic tumor phenotype. Oncogenic subversion of CRC TFs is well documented, but the role of loss of tumor suppressors plays remains unclear. Zinc-finger TF CASZ1 is a chromosome 1p36 (chr1p36) tumor suppressor. Single-cell RNA sequencing data analyses indicate that CASZ1 is highly expressed in developing chromaffin cells coincident with an expression of NB CRC TFs. In NB tumor cells, the CASZ1 tumor suppressor is silenced while CRC components are highly expressed. We find the NB CRC component HAND2 directly represses CASZ1 expression. ChIP-seq and transcriptomic analyses reveal that restoration of CASZ1 upregulates noradrenergic neuronal genes and represses expression of CRC components by remodeling enhancer activity. Our study identifies that the restored CASZ1 forms a negative feedback regulatory circuit with the established NB CRC to induce noradrenergic neuronal differentiation of NB.

China and Russia aim to increase bilateral trade to 200 billion USD by 2024. In addition to the enormous potential for cooperation in the field of traditional energy and mineral products, agriculture, investment and engineering contracts, as well as scientific and technological cooperation, have developed rapidly. The latter is expected to become a new pillar of Sino-Russian economic and trade cooperation. The subject of this study is the ongoing innovation in the banking sector in the organization of settlements in the yuan between Russia and China. The international system of settlements and payments includes the transfer of financial information and the distribution of assets, it is a key link in global economic cooperation. However, the Sino-Russian system of payments and settlements is severely restricted by the United States. Against the background of abuse of the US financial hegemony and acceleration of internationalization of the yuan, the settlement system between China and Russia faces real demand for dedollarization, which lead to mutual settlements between China and Russia in the national currency, especially the RMB calculations. Based on the analysis of the actual and potential demand for Chinese yuan in the Russian market, the political environment of settlements in yuan and the technical conditions for calculating the amount, the authors concluded that the prospects for the Sino-Russian system of settlements and payments in yuan are high.

Low temperature inhibits the regeneration of amputated tails of Gekko japonicus by influencing the energy sensory Akt/mTOR pathway, which is also modulated by injury-induced Wnt signal.

In this paper, we study the shape of the bifurcation curves of positive solutions for the one-dimensional Minkowski-curvature problem. By developing some new time mapping techniques, we find that the bifurcation curve is ⊂-shaped/monotone increasing/S-like shaped on the (λ,||u||∞) plane when the nonlinearity satisfies different assumptions. Finally, two examples are given to illustrate our result.

BackgroundChronic pressure overload triggers pathological cardiac hypertrophy that eventually leads to heart failure. Effective biomarkers and therapeutic targets for heart failure remain to be defined. The aim of this study is to identify key genes associated with pathological cardiac hypertrophy by combining bioinformatics analyses with molecular biology experiments.MethodsComprehensive bioinformatics tools were used to screen genes related to pressure overload-induced cardiac hypertrophy. We identified differentially expressed genes (DEGs) by overlapping three Gene Expression Omnibus (GEO) datasets (GSE5500, GSE1621, and GSE36074). Correlation analysis and BioGPS online tool were used to detect the genes of interest. A mouse model of cardiac remodeling induced by transverse aortic constriction (TAC) was established to verify the expression of the interest gene during cardiac remodeling by RT-PCR and western blot. By using RNA interference technology, the effect of transcription elongation factor A3 (Tcea3) silencing on PE-induced hypertrophy of neonatal rat ventricular myocytes (NRVMs) was detected. Next, gene set enrichment analysis (GSEA) and the online tool ARCHS4 were used to predict the possible signaling pathways, and the fatty acid oxidation relevant pathways were enriched and then verified in NRVMs. Furthermore, the changes of long-chain fatty acid respiration in NRVMs were detected using the Seahorse XFe24 Analyzer. Finally, MitoSOX staining was used to detect the effect of Tcea3 on mitochondrial oxidative stress, and the contents of NADP(H) and GSH/GSSG were detected by relevant kits.ResultsA total of 95 DEGs were identified and Tcea3 was negatively correlated with Nppa, Nppb and Myh7. The expression level of Tcea3 was downregulated during cardiac remodeling both in vivo and in vitro. Knockdown of Tcea3 aggravated cardiomyocyte hypertrophy induced by PE in NRVMs. GSEA and online tool ARCHS4 predict Tcea3 involved in fatty acid oxidation (FAO). Subsequently, RT-PCR results showed that knockdown of Tcea3 up-regulated Ces1d and Pla2g5 mRNA expression levels. In PE induced cardiomyocyte hypertrophy, Tcea3 silencing results in decreased fatty acid utilization, decreased ATP synthesis and increased mitochondrial oxidative stress.ConclusionOur study identifies Tcea3 as a novel anti-cardiac remodeling target by regulating FAO and governing mitochondrial oxidative stress.