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Objective The co-structure system of subway station (hereinafter referred to as 'co-structure system') realizes the connection and conversion between the box structure and the box frame structure through thick plates. Due to the unique structural form of the co-structural system, its seismic response law is currently unclear, further study on the characteristics of its seismic response is needed. Method Taking the co-structure system of a comprehensive utility tunnel and subway station as an example, the finite element simulation model of soil-co-structure system interaction is established. Considering one-way and two-way seismic waves (both horizontal and vertical) as inputs, three working conditions are selected. The acceleration response characteristics, displacement response characteristics, compressive and tensile damage situations, and the evolution process of the co-structure system under seismic action are analyzed. Taking the left column end of the co-structure system as an example, the internal force response characteristics of some structural parts are discussed. Result & Conclusion The vertical acceleration of the co-structure system is greatly affected by the bidirectional coupling ground motion. The maximum increase in acceleration at the joint between the side wall and the negative first floor slab reaches 158 % (compared with the vertical ground motion). Vertical ground motion may increase the relative horizontal and relative vertical displacements in the roof and floor of the co-structure system, and the internal force response of the column as well. Locations of the co-structure system such as the column ends, the lower part of the side wall, both ends of the bottom plate, the connection of the components, and the axillary angle are vulnerable to seismic damage, and should be strengthened accordingly.

Abstract Background Nowadays, companion and working dogs hold significant social and economic importance. Dry eye, also known as dry keratoconjunctivitis (KCS), a common disease in ophthalmology, can readily impact a dog’s working capacity and lead to economic losses. Although there are several medications available for this disease, all of them only improve the symptoms on the surface of the eye, and they are irritating and not easy to use for long periods of time. Adipose-derived mesenchymal stem cells (ADMSC) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of ADMSC. Here, we aimed to use ADMSC overexpressing Secreted Protein Acidic and Rich in Cysteine (SPARC) to treat 0.25% benzalkonium chloride-treated dogs with dry eye to verify its efficacy. For in vitro validation, we induced corneal epithelial cell (HCECs) damage using 1 µg/mL benzalkonium chloride. Methods Fifteen male crossbred dogs were randomly divided into five groups: normal, dry eye self-healing control, cyclosporine-treated, ADMSC-CMV-treated and ADMSC-OESPARC-treated. HCECs were divided into four groups: normal control group, untreated model group, ADMSC-CMV supernatant culture group and ADMSC-OESRARC supernatant culture group. Results SPARC-modified ADMSC had the most significant effect on canine ocular surface inflammation, corneal injury, and tear recovery, and the addition of ADMSC-OESPARC cell supernatant also had a salvage effect on HCECs cellular damage, such as cell viability and cell proliferation ability. Moreover, analysis of the co-transcriptome sequencing data showed that SPARC could promote corneal epithelial cell repair by enhancing the in vitro viability, migration and proliferation and immunosuppression of ADMSC. Conclusion The in vitro cell test and in vivo model totally suggest that the combination of SPARC and ADMSC has a promising future in novel dry eye therapy. Graphical abstract

ABSTRACTMany biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-β signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.

Abstract Smart windows effectively respond to the ever‐changing climatic conditions, offering a smart solution for low‐carbon buildings. However, current smart windows derived from chromic materials often have inferior solar modulation ability, or showcase high haze that obstructs outdoor views. Here, instead of developing new chromic materials, a new bistatic window is proposed for ultra‐high solar modulation and luminous transmission. The new developed window can reduce the indoor surface temperature for ≈11 °C, and reduce the building space cooling and heating energy consumption by 30% to 40%, providing significant energy‐related advances over traditional smart windows. In detail, the bistatic window exhibits excellent solar modulation ability (ΔTsol = 61%), high visible transmittance in both bleached (Tlum,bleached = 91%) and colored (Tlum,colored = 56%) states, low haze (< 1%), rapid switching response (switching time < 1 min), high color rendering index (CRI > 80), and long‐cyclic stability after 1000 cycles. With the advantages of facile fabrication and scalability, it is foreseen the developed bistatic window holds promising prospect for the next‐generation low‐carbon buildings, paving a new way for future advancements in the fields of smart windows.

Abstract Background Novel biomarkers are required in gastric cancer (GC) treated by immunotherapy. Epstein-Barr virus (EBV) infection induces an immune-active tumor microenvironment, while its association with immunotherapy response is still controversial. Genes underlying EBV infection may determine the response heterogeneity of EBV + GC. Thus, we screened hub genes associated with EBV infection to predict the response to immunotherapy in GC. Methods Prognostic hub genes associated with EBV infection were screened using multi-omic data of GC. EBV + GC cells were established and confirmed by EBV-encoded small RNA in situ hybridization (EBER-ISH). Immunohistochemistry (IHC) staining of the hub genes was conducted in GC samples with EBER-ISH assay. Infiltrating immune cells were stained using immunofluorescence. Results CHAF1A was identified as a hub gene in EBV + GC, and its expression was an independent predictor of overall survival (OS). EBV infection up-regulated CHAF1A expression which also predicted EBV infection well. CHAF1A expression also predicted microsatellite instability (MSI) and a high tumor mutation burden (TMB). The combined score (CS) of CHAF1A expression with MSI or TMB further improved prognostic stratification. CHAF1A IHC score positively correlated with the infiltration of NK cells and macrophages M1. CHAF1A expression alone could predict the immunotherapy response, but its CS with EBV infection, MSI, TMB, or PD-L1 expression showed better effects and improved response stratification based on current biomarkers. Conclusions CHAF1A could be a novel biomarker for immunotherapy of GC, with the potential to improve the efficacy of existing biomarkers.

The oil and gas exploration of the Middle and Lower Cambrian in the Tarim Basin reveals widely distributed source rocks with the Yuertusi Formation being recognized as high-quality source rocks that are distributed in a rather small range. The Xiaoerbulake Formation that is right under the Yuertusi Formation has also been eyed as potential high-quality source rocks and is studied through analyses focusing on the stratigraphic development, the abundance, type, and maturity of organic matter, and the paleoproductivity of a dark-colored algae dolomite within the formation. The results show that the dolomite is rich in organic matter of mainly types I and II kerogens. Although reached the high mature to over-mature stage, the dolomite was deposited in an anoxic sedimentary environment featuring a high paleoproductivity level and a high organic carbon burial efficiency, quite favorable for the development of high-quality source rocks. The study provides material evidence to the Middle-Lower Cambrian subsalt source rock-reservoir-caprock combination model for the Tarim Basin.

The Cambrian subsalt dolomite in the Kalpin area of the Tarim Basin is an important reserve growth point and strategic replacement area. However, there is a lack of clear understanding regarding the formation mechanism of high-quality reservoirs in this region, which has hindered oil and gas exploration. This study aims to address this knowledge gap by providing a comprehensive description of the rock types and characteristics of the Xiao'erbulak Formation. Microscope observations, geochemical analyses, and interpretations of well logging data from Well KPN1 were used in this analysis. The Xiao'erbulak Formation can be divided into four members, arranged from bottom to top. The relatively high manganese (Mn) content (87–137.7 ppm), oxygen isotope composition (δ18O) with an average value of −6.37‰, and strontium isotope ratio (87Sr/86Sr) with an average value of 0.7109 indicate that dolomitization of the Xiao'erbulak Formation likely occurred during the penecontemporaneous-shallow burial period. The early formation of dolomite contributed to increased reservoir porosity and resistance to compaction during deep burial, which laid the foundation for reservoir formation. The carbon isotope composition (δ13C) of the Xiao 1 and Xiao 2 members exhibit frequent zigzag curves, indicating recurring progression/regression processes. The subsequent development of granular beach facies played a crucial role in reservoir formation in the Xiao 2 Member. Tectonic fractures and penecontemporaneous karstification controlled the reservoir characteristics of the Xiao 3 Member. Furthermore, this study provides an analysis of the diagenetic evolution model of Well KPN1 and examines the impact of diagenetic transformations on reservoir quality. The systematic analysis of downhole data from Well KPN1 serves as a foundational reference for comparative studies with other drilling sites in the area. It also offers valuable guidance for future exploration and deployment strategies in the northwest Tarim Basin.

The integration of large-scale photovoltaics (PVs) into the power grid has significantly altered the transient synchronization dynamics of traditional power systems dominated by synchronous generators (SGs) and posed great challenges to modeling and analysis of PVs integration. In this paper, the transient synchronization stability of the PV-SG system is studied using the singular perturbation technique. Firstly, a nonlinear model of a PV-SG system is established to reveal the multiscale transient synchronization characteristics. Further, the full system is decomposed into a slow subsystem and a fast subsystem by the singular perturbation technique. The fast subsystem containing the dynamics of the DC voltage control, terminal voltage control, and phase-locked loop, and the slow subsystem containing the dynamics of rotor motion can perfectly reflect the dynamics of the full system within the electromagnetic and electromechanical timescales, respectively. The proposed model provides a clearer physical picture of dynamics in the PV-SG system within the electromagnetic and electromechanical timescales. Subsequently, the stability of the slow and fast subsystems is investigated using the energy function and eigenvalue analysis methods, respectively. Meanwhile, the impacts of various operating, control, and structural parameters on the transient synchronization stability are uncovered. Different from the most existing research endeavors on the wide simulations of the PVs integration, the impact of PVs on the synchronization dynamics of SGs without considering the dynamical characteristics of the PV system, and the transient synchronization stability analyses of the PLL-based voltage source converter systems, it is the key contribution to study the transient synchronization dynamical characteristics of the PV system and its interaction with the SG under different timescales. All these are helpful and easy to extend to more complicated PV-SG systems. Finally, the analysis results are validated by extensive simulations.

BackgroundMobile phone addiction has a high detection rate among adolescents and is thought to be related to academic stress. However, the underlying mechanisms in this relation were still unclear. The present study tested the mediating role of psychological distress and the moderating roles of peer alienation and rumination in the relationship between academic stress and mobile phone addiction.MethodsA total of 742 middle school students were recruited to complete measures of academic stress, psychological distress, mobile phone addiction, peer alienation, rumination, and demographic variables. Regression-based statistical mediation and moderation were conducted using the PROCESS macro for SPSS.ResultsThe results indicated that academic stress was significantly and positively associated with mobile phone addiction, and this link could be mediated by psychological distress. Moreover, this indirect effect was moderated by both peer alienation and rumination. Specifically, the mediating effect of psychological distress was stronger for adolescents with higher levels of peer alienation or adolescents with higher levels of rumination, as well as those with both higher levels of peer alienation and rumination.ConclusionThe findings of this study enrich our understanding of how and for whom academic stress is correlated with mobile phone addiction. Education experts and parents should pay special attention to adolescents suffering from academic stress, especially those with higher peer alienation and rumination, and help them get rid of mobile phone addiction.

N6-methyladenosine (m6A) methylation modification is a ubiquitous RNA modification involved in the regulation of various cellular processes, including regulation of RNA stability, metabolism, splicing and translation. Gastrointestinal (GI) cancers are some of the world’s most common and fatal cancers. Emerging evidence has shown that m6A modification is dynamically regulated by a complex network of enzymes and that the catalytic subunit m6A-METTL complex (MAC)-METTL3/14, a core component of m6A methyltransferases, participates in the development and progression of GI cancers. Furthermore, it has been shown that METTL3/14 modulates immune cell infiltration in an m6A-dependent manner in TIME (Tumor immune microenvironment), thereby altering the response of cancer cells to ICIs (Immune checkpoint inhibitors). Immunotherapy has emerged as a promising approach for treating GI cancers. Moreover, targeting the expression of METTL3/14 and its downstream genes may improve patient response to immunotherapy. Therefore, understanding the role of MAC in the pathogenesis of GI cancers and its impact on immune cell infiltration may provide new insights into the development of effective therapeutic strategies for GI cancers.

BackgroundAberrant metabolism is a major hallmark of cancers and hereditary diseases. Genes associated with inborn metabolic errors may also play roles in cancer development. This study evaluated the overall impact of these genes on gastric cancer (GC).MethodsIn total, 162 genes involved in 203 hereditary metabolic diseases were identified in the Human Phenotype Ontology database. Clinical and multi-omic data were acquired from the GC cohort of the Affiliated Hospital of Jiangsu University and other published cohorts. A 4-gene and 32-gene signature was established for diagnosis and prognosis or therapeutic prediction, respectively, and corresponding abnormal metabolism scores (AMscores) were calculated.ResultsThe diagnostic AMscore showed high sensitivity (0.88-1.00) and specificity (0.89-1.00) to distinguish between GC and paired normal tissues, with area under the receiver operating characteristic curve (AUC) ranging from 0.911 to 1.000 in four GC cohorts. The prognostic or predictive AMscore was an independent predictor of overall survival (OS) in five GC cohorts and a predictor of the OS and disease-free survival benefit of postoperative chemotherapy or chemoradiotherapy in one GC cohort with such data. The AMscore adversely impacts immune biomarkers, including tumor mutation burden, tumor neoantigen burden, microsatellite instability, programmed death-ligand 1 protein expression, tumor microenvironment score, T cell receptor clonality, and immune cell infiltration detected by multiplex immunofluorescence staining. The AUC of the AMscore for predicting immunotherapy response ranging from 0.780 to 0.964 in four cohorts involving GC, urothelial cancer, melanoma, and lung cancer. The objective response rates in the low and high AMscore subgroups were 78.6% and 3.2%, 40.4% and 7%, 52.6% and 0%, and 72.7% and 0%, respectively (all p

BackgroundLoneliness and mobile phone addiction are common phenomena in our daily life that can lead to physical and psychological maladaptation. Although loneliness has been considered to be correlated with adolescents' mobile phone addiction, the underlying mechanisms of the relation between loneliness and mobile phone addiction are still unclear. In order to address the problem of mobile phone addiction among adolescents, the association of loneliness with mobile phone addiction was explored from the perspective of Compensatory Internet Use Theory. The mediating role of anthropomorphism and the moderating role of family support were examined.MethodsData were collected through convenience sampling from a comprehensive university in China. A total of 582 Chinese college students (279 men and 303 women), aged from 17 to 24 (Mage = 20.22 years, SD = 1.46), participated in this study. Their loneliness, anthropomorphism, family support and mobile phone addiction were measured using well-validated self-report questionnaires. Regression-based statistical mediation and moderation were conducted using the PROCESS macro for SPSS.ResultsLoneliness was significantly and positively associated with mobile phone addiction, and this link could be mediated by anthropomorphism. Moreover, the direct effect of loneliness on mobile phone addiction and the indirect effect of anthropomorphism in this link were moderated by family support. Both these two effects were stronger for college students with lower family support.ConclusionThe present study broadened our knowledge of the underlying mechanisms between loneliness and mobile phone addiction. These findings may contribute to a better understanding of the impact loneliness can have on mobile phone addiction as well as its paths. Moreover, the results can also provide advice for parents and constructive suggestions for rationalizing college students' mobile phone use in the mobile Internet era. Educational professionals and parents should pay special attention to the problem of mobile phone addiction among lonely adolescents, especially for those with low family support.

The high production cost and poor electrochemical performance of polyanionic cathode hinders their industrial application. Here, the authors report large-scale fabrication of sodium vanadium fluorophosphates and in situ construction of their carbon nanocomposites via a mechanochemical protocol.

Synchronous stability in power systems is of essential importance for system safety and operation. For the phase-locked loop (PLL)-based synchronous stability in power electronic-based power systems, which has recently stimulated interest in researchers in the field of electrical power engineering, but is still controversial, this paper divides the topic into two aspects, including the PLL device stability and the system stability. It is found that the PLL device is always stable and the error between the PLL output angle θpll and the terminal voltage angle θt is always finite. Therefore, the synchronization of power electronic-based power systems should be understood as the output synchronization between the electrical rotation vectors (θt or θpll) from each item of grid-tied equipment, rather than the synchronization of the PLL device itself. In addition, it is found that θpll plays an active role in the system synchronization dynamics not only in electromagnetic timescales but also electromechanical timescales and it could be selected as a dominant observable. In this paper, the concept of synchronous stability is well clarified. These findings are well supported by theoretical analyses and MATLAB/Simulink simulations, and thus could provide insights on the synchronous stability mechanism.

The sea temperature has been observed to chronically increase during the past decades, leaving unpredictable influences to the marine biological resources. Thus, it is of vital significance to study the biological responses of ocean inhabited organisms with the artificially stimulated heat stress environment. Cynoglossus semilaevis provides us with an ideal model to study the influence of chronic heat stress on the sexual differentiation in marine teleosts for its genetic sex determination (GSD) + environmental effected (EE) sex determination system. In this study, the comparative experiment was conducted employing heated seawater (HT group) and ambient seawater (CT group) to cultivate juvenile C. semilaevis respectively. Significant differences were exhibited in growth performance and a delayed germ cell development effect was found in pseudomales formed under chronic heat stress. Using transcriptome analysis, the transcription profile of 55 days post fertilization (dpf) and 100 dpf juveniles’ gonads were studied. A total of 47 libraries were constructed with an average mapping rate of 94.63% after assembling. GO and KEGG enrichment were proceeded using DEGs screened out between (1) pseudomale gonads at 55 dpf and 100 dpf in HT and CT group (2) pseudomale and female gonads at 55 dpf and 100 dpf in HT and CT group. Terms and pathways involved in steroid stimulation, reproduction ability, germ cell proliferation et al. were shed light on. The expression pattern of 29 DEGs including amh, hsp90b1, pgr et al. were also provided to supplement the results of functional enrichment. Weighted gene co-expression networks analysis (WGCNA) was constructed and hspb8-like, histone H2A.V were exhibited to play vital roles in the heat-induced masculinization. Our findings facilitate the understanding for transcriptional variations in intensive masculinization cause by chronic heat stress of C. semilaevis and provide referable study of the influences on the teleosts in elevated sea temperature.

Predicting the drug response of patients with cancer is crucial for implementing targeted therapy. Here, Su et al. make patient-derived cell lines and perform targeted sequencing and RNA-seq to identify CDKN2A/2B loss as a predictor of response to CDK4/6 inhibitors in esophageal squamous cell carcinoma.

Damping has a significant influence on the calculation of structural seismic response. In this paper, we compare the commonly used viscous damping (Rayleigh damping (RD) and Caughey damping (CD)) in combination with the isolated structure test. To avoid the arbitrariness of choosing two reference vibration frequencies in constructing RD, all the combinations of the first several vibration frequencies were calculated. Because the material characteristics of the isolation layer and the superstructure are significantly different and the deformation of the isolation layer is large, we construct nonproportional damping according to these two kinds of damping and make a comparative analysis. Analyzing experimental data, we can obtain the optimal frequency combination of RD and nonproportional damping during dynamic analysis of the isolated structure, the priority order of choosing damping models. For the calculation of RD, the 1st modal frequency of the structure should be included, and the 2nd and 3rd modal frequencies of the nonisolated structure are proposed to calculate the nonproportional damping based on Rayleigh damping (NP-RD) for the three-story frame structure in this paper. RD and nonproportional damping based on Caughey damping (NP-CD) are firstly recommended to be used in the calculation of the isolated structure, followed by NP-RD and then CD.

Background. Increased blood pressure (BP) variability may worsen the prognosis of stroke. This study aimed at investigating the association between BP variability and early functional prognosis in patients with pontine infarction. Methods. According to types of pontine infarction, all the 137 patients were divided into two groups: 70 patients with paramedian pontine infarction (PPI) and 67 patients with deep pontine infarction (DPI). Common risk factors, 24-hour continuous blood pressure monitoring data, and the coefficient of variation were collected after admission in the hospital. Functional outcomes were evaluated with modified Rankin scale (mRS) at 3 months after discharge (favorable outcome: mRS scores ≤ 2; poor outcome: mRS scores > 2). Results. The level of Glu, HbA1c, LDL, and NIHSS scores in the PPI group was significantly higher than that in the DPI group, and the concentration of blood uric acid was lower in the PPI group. Diastolic pressure in the PPI group is significantly higher than that in the DPI group, and coefficient of variation (CV) of systolic pressure in PPI is higher when compared with DPI ((88.77 ± 1.71) mmHg vs. (80.74 ± 1.31) mmHg; (11.54 ± 0.35) vs. (10.24 ± 0.25)). In multivariate analyses, the CV of systolic pressure, diastolic pressure, NIHSS scores, and the paramedian pontine infarction was independently associated with 3-month clinical outcome (OR = 1.94, 95% CI = 1.252–2.994, P=0.003; OR = 1.08, 95% CI = 1.002–1.166, P=0.04; OR = 1.58, 95% CI = 1.164–2.159, P=0.003; OR = 9.87, 95% CI = 1.045–32.193, P=0.04). Conclusion. In conclusion, increased 24-hour (BP) variability, NIHSS scores, and paramedian pontine were associated with early poor prognosis in patients with acute pontine infarction.

Abstract Background This study aims to analyze the clinical, imaging, electrophysiological, and dermatopathological features of a patient with adult‐onset neuronal intranuclear inclusion disease (NIID) and to explore the diagnostic methods of adult‐onset NIID. Case presentation We here report a 63‐year‐old male with recurrent acute encephalopathy syndrome and autonomic nervous system damage syndrome characterized by sexual dysfunction and urinary and fecal dysfunction. Cranial diffusion‐weighted magnetic resonance imaging (DWI) demonstrated symmetrically distributed strip‐shaped high‐intensity signal in bilateral fronto‐occipital‐parietal cortical‐medullary junction. Electrophysiological test revealed that the main site of injury was myelin sheath in both motor and sensory nerves. Skin biopsy revealed eosinophilic spherical inclusion bodies in the nucleus of sweat gland epithelial cells. Conclusion This case suggests that adult NIID is a chronic neurodegenerative disease with high clinical heterogeneity. Subcortical strip‐shaped high‐intensity signal on DWI has high diagnostic significance. Eosinophilic intranuclear inclusion bodies detected by skin biopsy contribute to diagnosis.

Abstract Background Intron retention (IR), the most prevalent alternative splicing form in plants, plays a critical role in gene expression during plant development and stress response. However, the molecular mechanisms underlying IR regulation remain largely unknown. Results Knockdown of SDG725, a histone H3 lysine 36 (H3K36)-specific methyltransferase in rice, leads to alterations of IR in more than 4700 genes. Surprisingly, IR events are globally increased at the 5′ region but decreased at the 3′ region of the gene body in the SDG725-knockdown mutant. Chromatin immunoprecipitation sequencing analyses reveal that SDG725 depletion results in a genome-wide increase of the H3K36 mono-methylation (H3K36me1) but, unexpectedly, promoter-proximal shifts of H3K36 di- and tri-methylation (H3K36me2 and H3K36me3). Consistent with the results in animals, the levels of H3K36me1/me2/me3 in rice positively correlate with gene expression levels, whereas shifts of H3K36me2/me3 coincide with position-specific alterations of IR. We find that either H3K36me2 or H3K36me3 alone contributes to the positional change of IR caused by SDG725 knockdown, although IR shift is more significant when both H3K36me2 and H3K36me3 modifications are simultaneously shifted. Conclusions Our results revealed that SDG725 modulates IR in a position-specific manner, indicating that H3K36 methylation plays a role in RNA splicing, probably by marking the retained introns in plants.

Abstract Natural antisense transcripts (NAT) and alternative polyadenylation (APA) of messenger RNA (mRNA) are important contributors of transcriptome complexity, each playing a critical role in multiple biological processes. However, whether they have crosstalk and function collaboratively is unclear. We discovered that APA enriched in human sense-antisense (S-AS) gene pairs, and finally focused on RNASEH2C-KAT5 S-AS pair for further study. In cis but not in trans over-expression of the antisense KAT5 gene promoted the usage of distal polyA (pA) site in sense gene RNASEH2C, which generated longer 3′ untranslated region (3′UTR) and produced less protein, accompanying with slowed cell growth. Mechanistically, elevated Pol II occupancy coupled with SRSF3 could explain the higher usage of distal pA site. Finally, NAT-mediated downregulation of sense gene’s protein level in RNASEH2C-KAT5 pair was specific for human rather than mouse, which lacks the distal pA site of RNASEH2C. We provided the first evidence to support that certain gene affected phenotype may not by the protein of its own, but by affecting the expression of its overlapped gene through APA, implying an unexpected view for understanding the link between genotype and phenotype.

Powdery mildew (PM) is one of the most destructive diseases that threaten cucumber production globally. Efficient breeding of novel PM-resistant cultivars will require a robust understanding of the molecular mechanisms of cucumber resistance against PM. Using a genome-wide association study, we detected a locus significantly correlated with PM resistance in cucumber stem, pm-s5.1. A 1449-bp insertion in the CsMLO8 coding region at the pm-s5.1 locus resulted in enhanced stem PM resistance. Knockout mutants of CsMLO8 and CsMLO11 generated by CRISPR/Cas9 both showed improved PM resistance in the stem, hypocotyl, and leaves, and the double mutant mlo8mlo11 displayed even stronger resistance. We found that reactive oxygen species (ROS) accumulation was higher in the stem of these mutants. Protein interaction assays suggested that CsMLO8 and CsMLO11 could physically interact with CsRbohD and CsCRK2, respectively. Further, we showed that CsMLO8 and CsCRK2 competitively interact with the C-terminus of CsRbohD to affect CsCRK2-CsRbohD module-mediated ROS production during PM defense. These findings provide new insights into the understanding of CsMLO proteins during PM defense responses.

BACKGROUND: The plant root system is critical for the absorption of water and nutrients, and have a direct influence on growth and yield. In cucumber, a globally consumed crop, the molecular mechanism of root development remains unclear, and this has implications for developing stress tolerant varieties. This study sought to determine the genetic patterns and related genes of cucumber root weight. A core cucumber germplasms population was used to do the GWAS analysis in three environments. RESULTS: Here, we investigated four root-weight related traits including root fresh weight (RFW), root dry weight (RDW), ratio of root dry weight to root fresh weight (RDFW) and the comprehensive evaluation index, D-value of root weight (DRW) deduced based on the above three traits for the core germplasm of the cucumber global repository. According to the D-value, we identified 21 and 16 accessions with light and heavy-root, respectively. We also found that the East Asian ecotype accessions had significantly heavier root than other three ecotypes. The genome-wide association study (GWAS) for these four traits reveals that 4 of 10 significant loci (gDRW3.1, gDRW3.2, gDRW4.1 and gDRW5.1) were repeatedly detected for at least two traits. Further haplotype and expression analysis for protein-coding genes positioned within these 4 loci between light and heavy-root accessions predicted five candidate genes (i.e., Csa3G132020 and Csa3G132520 both encoding F-box protein PP2-B1 for gDRW3.1, Csa3G629240 encoding a B-cell receptor-associated protein for gDRW3.2, Csa4G499330 encodes a GTP binding protein for gDRW4.1, and Csa5G286040 encodes a proteinase inhibitor for gDRW5.1). CONCLUSIONS: We conducted a systematic analysis of the root genetic basis and characteristics of cucumber core germplasms population. We detected four novel loci, which regulate the root weight in cucumber. Our study provides valuable candidate genes and haplotypes for the improvement of root system in cucumber breeding.

In Chinese, writing is a basic competency that pupils should possess. But it is still challenging for teachers to improve pupils' writing abilities. Therefore, this study proposes an intelligence-based cognitive diagnostic feedback strategy to improve pupils' writing ability and writing learning quality by analyzing their writing performance, epistemic network structure, and learning engagement. Thepupils are randomly divided into an experimental group (N = 28) and a control group (N = 28). The experimental group adopts the ICDF strategy, while the control group adopts the WS-TF strategy. The results showed that the I-CDF strategy improved the pupil's writing scores and learning engagement. In addition, the results of the epistemic network analysis showed that the pupils using the ICDF strategy focused on dynamic descriptions such as action, psychology, and environmental changes in vocabulary use, and the epistemic network structure was more complex than the control group. The interviews showed that the pupils in the experimental group were highly satisfied with I-CDF strategy.

This paper investigates the valuation of vulnerable European options considering the market prices of common systematic jump risks under regime-switching jump-diffusion models. The way of regime-switching Esscher transform is adopted to identify an equivalent martingale measure for pricing vulnerable European options. Explicit analytical pricing formulae for vulnerable European options are derived by risk-neutral pricing theory. For comparison, the other two cases are also considered separately. The first case considers all jump risks as unsystematic risks while the second one assumes all jumps risks to be systematic risks. Numerical examples for the valuation of vulnerable European options are provided to illustrate our results and indicate the influence of the market prices of jump risks on the valuation of vulnerable European options.

Low temperatures (LTs) negatively affect the percentage and rate of cucumber (Cucumis sativus L.) seed germination, which has deleterious effects on yield. Here, a genome-wide association study (GWAS) was used to identify the genetic loci underlying low temperature germination (LTG) in 151 cucumber accessions that represented seven diverse ecotypes. Over two years, phenotypic data for LTG i.e., relative germination rate (RGR), relative germination energy (RGE), relative germination index (RGI) and relative radical length (RRL), were collected in two environments, and 17 of the 151 accessions were found to be highly cold tolerant using cluster analysis. A total of 1,522,847 significantly associated single-nucleotide polymorphism (SNP) were identified, and seven loci associated with LTG, on four chromosomes, were detected: gLTG1.1, gLTG1.2, gLTG1.3, gLTG4.1, gLTG5.1, gLTG5.2, and gLTG6.1 after resequencing of the accessions. Of the seven loci, three, i.e., gLTG1.2, gLTG4.1, and gLTG5.2, showed strong signals that were consistent over two years using the four germination indices, and are thus strong and stable for LTG. Eight candidate genes associated with abiotic stress were identified, and three of them were potentially causal to LTG: CsaV3_1G044080 (a pentatricopeptide repeat-containing protein) for gLTG1.2, CsaV3_4G013480 (a RING-type E3 ubiquitin transferase) for gLTG4.1, and CsaV3_5G029350 (a serine/threonine-protein kinase) for gLTG5.2. The function for CsPPR (CsaV3_1G044080) in regulating LTG was confirmed, as Arabidopsis lines ectopically expressing CsPPR showed higher germination and survival rates at 4°C compared to the wild-type, which preliminarily illustrates that CsPPR positively regulates cucumber cold tolerance at the germination stage. This study will provide insights into cucumber LT-tolerance mechanisms and further promote cucumber breeding development.

The pricing problem of geometric average Asian option under fractional Brownian motion is studied in this paper. The partial differential equation satisfied by the option’s value is presented on the basis of no-arbitrage principle and fractional formula. Then by solving the partial differential equation, the pricing formula and call-put parity of the geometric average Asian option with dividend payment and transaction costs are obtained. At last, the influences of Hurst index and maturity on option value are discussed by numerical examples.

Geometric-average Asian option pricing model with monotonous transaction cost rate under fractional Brownian motion was established. The method of partial differential equations was used to solve this model and the analytical expressions of the Asian option value were obtained. The numerical experiments show that Hurst exponent of the fractional Brownian motion and transaction cost rate have a significant impact on the option value.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that repress their targets at post transcriptional level. Single Nucleotide Polymorphisms (SNPs) in miRNAs can lead to severe defects to the functions of miRNAs and might result in diseases. Although several studies have tried to identify the SNPs in human miRNA genes or only in the mature miRNAs, there are only limited endeavors to explain the distribution of SNPs in these important genes. After a genome-wide scan for SNPs in human miRNAs, we totally identified 1899 SNPs in 961 out of the 1527 reported miRNA precursors of human, which is the most complete list of SNPs in human miRNAs to date. More importantly, to explain the distributions of SNPs existed in human miRNAs, we comprehensively and systematically analyzed the identified SNPs in miRNAs from several aspects. Our results suggest that conservation, genomic context, secondary structure, and functional importance of human miRNAs affect the accumulations of SNPs in these genes. Our results also show that the number of SNPs with significantly different frequencies among various populations in the HapMap and 1000 Genome Project data are consistent with the geographical distributions of these populations. These analyses provide a better insight of SNPs in human miRNAs and the spreading of the SNPs in miRNAs in different populations.

Key messageThe CsGAI gene, identified by map-based, was involved in regulating seed germination in low temperature via the GA and ABA signaling pathways. Low temperature reduces the percentage of seeds germinating and delays seed germinating time, thus posing a threat to cucumber production. However, the molecular mechanism regulating low temperature germination in cucumber is unknown. We here dissected a major quantitative trait locus qLTG1.1 that controls seed germination at low temperature in cucumber. First, we fine-mapped qLTG1.1 to a 46.3-kb interval, containing three candidate genes. Sequence alignment and gene expression analysis identified Csa1G408720 as the gene of interest that was highly expressed in seeds, and encoded a highly conserved, low temperature-regulated DELLA family protein CsGAI. GUS expression analysis indicated that higher promoter activity underscored higher transcriptional expression of the CsGAI gene. Consistent with the known roles of GAI in ABA and GA signaling during germination, genes involved in the GA (CsGA2ox, CsGA3ox) and ABA biosynthetic pathways (CsABA1, CsABA2, CsAAO3 and CsNCED) were found to be differently regulated in the tolerant and sensitive genotypes under low temperatures, and this was reflected in differences in their ratio of GA-to-ABA. Based on these data, we proposed a working model explaining how CsGAI integrates the GA and ABA signaling pathways, to regulate cucumber seed germination at low temperature, thus providing new insights into this mechanism.