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Hidden disaster-causing factors in coal mines are key geological factors that restrict the safety, high efficiency, green and intelligent mining, and transparent geology is an important technical means to realize the detection of hidden disaster-causing factors in coal mines, among them, geological structure transparent exploration is the most important. In order to build a transparent exploration system for hidden disaster-causing factors of geological structure that applies to different geological conditions or coalfield areas, first, based on analysis of factors causing hidden structural disasters, technical system of rapid investigation of factors causing structural hidden disasters is put forward, which is based on the regional structural analysis and the joint investigation of the ground and underground, effectively delineate the mine geological structure anomaly development area and analyze its distribution law. Based on the previous borehole data and 3D seismic data, the coal seam thickness, fault structure and roof and floor structure undulation patterns are analyzed. Comprehensive technical means such as channel wave exploration, directional drilling, advanced geophysical prospecting, earthquake while mining/driving, cuttings recording, rapid realistic description of roadway are adopted, further realizing the gradual transparency of the geological structure of the mining face, adopting the methods of theoretical analysis, engineering analogy, numerical simulation, similar material simulation, field engineering verification. Correlation between geological structure types, attribute characteristics and mine disasters, such as coal seam thickness, coal rock mass structure, gas emission, gas pressure, roof strata behavior, is analyzed. Response law of gas parameters and roof/ground pressure disasters in different areas of the mining face passing through the fault structure under the mining condition is studied. Monitoring and early-warning of the hidden disaster-causing factors of the face structures are realized by selecting the threshold value of the characteristic parameters, and the digital expression of the different geological structures and their disaster attributes is realized by using the digital technology, 3D transparent display of hidden disaster-causing factors is realized by modeling software. The technical system of geological structure exploration with 4 levels of regional structure geology research, exploration of hidden disaster-causing factors, scientific evaluation of disaster-causing threat and geological structure transparency is constructed, and carried out engineering practice in Tunbao Coal Mine. the results show that the types of geological structures in coal mine are complex, and there are not only graben type, barrier type, echelon type and flexure type of fault structures, but also small-scale scouring zone, fault and fracture zone. Complex geological structure is the key geological factor to induce mine gas outburst, roof disaster, stress concentration and mine rock burst. The influence of faults on stress concentration of roadway is 10 ～ 15 m, and the influence on working face is 20 ~ 30 m. There are gas enrichment areas in the working face, the distribution of gas content and gas emission has obvious zonation, and the zonation is controlled by faults. The content of coal seam gas and the amount of gas emission show logarithmic correlation with the distance between the working face and the fault, and increase obviously at the distance of 25 m from the fault, and change little in the area of more than 25 m, in the region less than 25 m, it increases exponentially with the decrease of distance. 20 m before and after the first pressure position and 30 m after the face-to-face are medium impact danger areas, the coal pillar affected area in goaf, 50 m before and after the final line, and 30 m before and after the fault with drop greater than 4 m are weak impact risk areas. The overlapping area of hidden disaster-causing factors such as rock burst, roof and gas, is the key area of disaster prevention and control. The research result realizes seamless connection between the hidden disaster-causing factors of geological structure and the mine disaster, and provides a feasible technical path for the development of traditional geological exploration in coal mine area to digitalization and intelligentization.

BackgroundWhile the correlation between physical activity (PA) and mental health is well known, the mediating mechanism of resilience between the two variables remains unclear.ObjectivesTo systematically evaluate the relationship between PA and mental health, and explore the mediating role of resilience between them.MethodsA systematic search of electronic databases (PubMed, Web of Science, ProQuest, Ebsco, China Knowledge, and China Biomedical Database) was conducted to identify relevant studies, and meta-analytic procedures were used to assess the strength of the relationships between PA and mental health. Furthermore, a meta-analytic structural equation model (MASEM) was used to assess the mediating effects of resilience, ensuring the reliability of our findings.ResultsThe findings of 15 studies (17,043 subjects) were subjected to meta-analysis and route analysis. The findings of the meta-analysis revealed a statistically significant positive correlation of 0.288 (95% CI, 0.166–0.402) between PA and positive indicators of mental health, as well as a statistically significant negative correlation (95% CI, −0.342 to −0.171) with negative indicators of mental health. Furthermore, the results of MASEM path analysis indicated that PA may indirectly impact both positive and negative indicators of mental health through the mediating factor of resilience. The indirect effect values were 0.108 (95% CI, 0.080–0.141) and −0.074 (95% CI, −0.100 to −0.051), respectively, accounting for 40.15% of the total effect value and 28.91%.ConclusionPhysical activity is positively correlated with positive indicators of mental health and negatively correlated with negative indicators of mental health. Moreover, PA can positively influence mental health through the mediating role of resilience.

Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder. A retrospective analysis predicted that the live birth prevalence of SRS in Estonia is 1:15,886 [Yakoreva et al., Eur J Hum Genet, 2019, 27(11), 1649–1658]. The most common causative genetic mechanism in the proband is loss of paternal methylation in the imprinted control region 1 (ICR1) at 11p15.5 chromosome. A few studies suggested that inherited or de novo loss-of-function alterations of the PLAG1 gene, including the whole-gene deletion and intragenic pathogenic variants, could cause a rare type of SRS. To date, less than 20 unrelated PLAG1-related SRS cases have been reported, and the clinical information about these cases is limited. We report the first prenatal case of SRS with 8q12 deletion (including the PLAG1 gene). The fetus presented with intrauterine growth retardation, small for gestational age, relative macrocephaly at birth, and a protruding forehead. Unlike classical SRS cases, the fetus had micrognathia and did not show body asymmetry. We hope that the literature review in this study provides new insights into genotype–phenotype relationships of PLAG1-related SRS.

Lespedeza bicolor Turcz. (L. bicolor) honey, a monofloral honey, has garnered increased attention due to its origin in the L. bicolor plant. A previous study has shown that L. bicolor honey can ameliorate inflammation. In this study, we aimed to investigate the effects of L. bicolor honey extract and its biomarker (Trifolin) on DSS-induced ulcerative colitis (UC). Our results demonstrated that L. bicolor honey extract and Trifolin significantly increased the expression levels of the tight junction cytokines Claudin-1 and ZO-1. Additionally, they decreased the pro-inflammatory factors TNF-α and IL-6 and enhanced the antioxidant factors NQO1 and GSTA1. Based on metabolomic analyses, L. bicolor honey extract and Trifolin regulated the progression of UC by inhibiting ferroptosis. Mechanistically, they improved the levels of SOD and iron load, increased the GSH/GSSG ratio, reduced MDA content and ROS release, and upregulated the Nrf2/HO-1 pathway, thereby inhibiting DSS-induced UC. Moreover, the expression levels of ferroptosis-related genes indicated that they decreased FTL, ACSL4, and PTGS2 while increasing SLC7A11 expression to resist ferroptosis. In conclusion, our study found that L. bicolor honey improves DSS-induced UC by inhibiting ferroptosis by activating the Nrf2/HO-1 pathway. These findings further elucidate the understanding of anti-inflammatory and antioxidant activities of L. bicolor honey.

Abstract Josephson tunneling in twisted cuprate junctions provides a litmus test for the pairing symmetry, which is fundamental for understanding the microscopic mechanism of high temperature superconductivity. This issue is rekindled by experimental advances in van der Waals stacking and the proposal of an emergent d+id-wave. So far, all experiments have been carried out on Bi2Sr2CaCu2O8+x (Bi-2212) with double CuO2 planes but show controversial results. Here, we investigate junctions made of Bi2Sr2-xLaxCuO6+y (Bi-2201) with single CuO2 planes. Our on-site cold stacking technique ensures uncompromised crystalline quality and stoichiometry at the interface. Junctions with carefully calibrated twist angles around 45° show strong Josephson tunneling and conventional temperature dependence. Furthermore, we observe standard Fraunhofer diffraction patterns and integer Fiske steps in a junction with a twist angle of 45.0±0.2°. Together, these results pose strong constraints on the d or d+id-wave pairing and suggest an indispensable isotropic pairing component.

Bee pollen, derived from various plant sources, is renowned for its nutritional and bioactive properties, aroma, and taste. This study examined the bee pollen with the highest yield in China obtained from four plant species, namely Brassica campestris (Bc), Nelumbo nucifera (Nn), Camellia japonica (Cj), and Fagopyrum esculentum (Fe), using fast e-nose and e-tongue technology to analyze their flavor chemistry. Results showed substantial differences in scent profiles among the varieties, with distinct odor compounds identified for each, including n-butanol, decanal, and ethanol, in Bc, Nn, and Cj, respectively. The primary odorants in Fe consist of E-2-hexen-1-ol and (Z)-3-hexen-1-ol. Additionally, e-tongue analysis revealed seven distinct tastes in bee pollen samples: AHS, PKS, CTS, NMS, CPS, ANS, and SCS, with variations in intensity across each taste. The study also found correlations between taste components and specific odor compounds, providing insights for enhancing product quality control in bee pollen processing.

ObjectiveAs the global population ages, disability among the elderly presents unprecedented challenges for healthcare systems. However, limited research has examined whether dietary interventions like tea consumption may alleviate and prevent disability in older adults. As an important dietary therapy, the health benefits of tea drinking have gained recognition across research disciplines. Therefore, this study aimed to investigate the association between tea drinking habits and disability levels in the elderly Chinese population.MethodsLeveraging data from the 2008 to 2018 waves of the Chinese Longitudinal Healthy Longevity Survey, we disaggregated tea drinking frequency and activities of daily living (ADL) measures and deployed fixed-effect ordered logit models to examine the tea-disability association for the first time. We statistically adjusted for potential confounders and conducted stratified analyses to assess heterogeneity across subpopulations.ResultsMultivariable fixed-effect ordered logistic regression suggested tea drinking has protective effects against ADL disability. However, only daily tea drinking was associated with lower risks of basic activities of daily living (BADL) disability [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.41–0.92] and lower levels of instrumental activities of daily living (IADL) disability (OR = 0.78; 95% CI, 0.64–0.95). Stratified analyses indicated heterogeneous effects across age and income groups. Daily tea drinking protected against BADL (OR = 0.26 and OR = 0.28) and IADL disability (OR = 0.48 and OR = 0.45) for adults over 83 years old and high-income households, respectively.ConclusionWe found that drinking tea almost daily was protective against disability in elderly people, warranting further research into optimal dosages. Future studies should utilize more rigorous causal inference methods and control for confounders.

We investigate the evolutionary dynamics of the multiplayer, snowdrift-like game based on memory effects, in which cooperators and defectors interact with another type of player named as exiter. To avoid being exploited by defectors, the conservative exiters tend to drop out of a game and merely share quite minor returns. Results on the well-mixed populations indicate that the existence of exiters is less conducive to cooperation. Whereas, in networks with simplicial complexes, the memory effect can effectively inhibit evolution of defection and promote cooperation. Other outcomes with respect to the evolution of exiters and defectors, including the co-existence of all three types of players in the network and the favor of exiter, can be obtained by tuning the payoff to exit and the proportion of 1-simplices and 2-simplices. The current results provide insight into how mutual cooperation emerges in real networked populations, influenced by the memory-based exit options.

Understanding the rich electronic orders in cuprate superconductors provide insights into the mechanism of high-temperature superconductivity. Here, the authors report a distinct charge order with Little-Parks like resistance oscillations at magnetic fields up to 10 T and around T c in lightly doped Bi2Sr2CaCu2O8+x .

Downy mildew caused by the obligate parasite Hyaloperonospora brassicae is a devastating disease for Brassica species. Infection of Hyaloperonospora brassicae often leads to yellow spots on leaves, which significantly impacts quality and yield of pakchoi. In the present study, we conducted a comparative transcriptome between the resistant and susceptible pakchoi cultivars in response to Hyaloperonospora brassicae infection. A total of 1073 disease-resistance-related differentially expressed genes were identified using a Venn diagram. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these genes were mainly involved in plant−pathogen interaction, plant hormone signal transduction, and other photosynthesis-related metabolic processes. Analysis of the phytohormone content revealed that salicylic acid increased significantly in the resistant material after inoculation with Hyaloperonospora brassicae, whereas the contents of jasmonic acid, abscisic acid, and 1-aminocyclopropane-1-carboxylic acid decreased. Exogenous salicylic acid treatment also significantly upregulated Hyaloperonospora brassicae-induced genes, which further confirmed a crucial role of salicylic acid during pakchoi defense against Hyaloperonospora brassicae. Based on these findings, we suggest that the salicylic-acid-mediated signal transduction contributes to the resistance of pakchoi to downy mildew, and PAL1, ICS1, NPR1, PR1, PR5, WRKY70, WRKY33, CML43, CNGC9, and CDPK15 were involved in this responsive process. Our findings evidently contribute to revealing the molecular mechanism of pakchoi defense against Hyaloperonospora brassicae.

Hypocotyl length is a critical determinant for the efficiency of mechanical harvesting in pakchoi production, but the knowledge on the molecular regulation of hypocotyl growth is very limited. Here, we report a spontaneous mutant of pakchoi, lhy7.1, and identified its characteristics. We found that it has an elongated hypocotyl phenotype compared to the wild type caused by the longitudinal growth of hypocotyl cells. Different light quality treatments, transcriptome, and proteomic analyses were performed to reveal the molecular mechanisms of hypocotyl elongation. The data showed that the hypocotyl length of lhy7.1 was significantly longer than that of WT under red, blue, and white lights but there was no significant difference under dark conditions. Furthermore, we used transcriptome and label-free proteome analyses to investigate differences in gene and protein expression levels between lhy7.1 and WT. At the transcript level, 4568 differentially expressed genes (DEGs) were identified, which were mainly enriched in “plant hormone signal transduction”, “photosynthesis”, “photosynthesis–antenna proteins”, and “carbon fixation in photosynthetic organisms” pathways. At the protein level, 1007 differentially expressed proteins (DEPs) were identified and were mainly enriched in photosynthesis-related pathways. The comprehensive transcriptome and proteome analyses revealed a regulatory network of hypocotyl elongation involving plant hormone signal transduction and photosynthesis-related pathways. The findings of this study help elucidate the regulatory mechanisms of hypocotyl elongation in lhy7.1.

Cannabis has been used for centuries to treat pain. The antinociceptive activity of tetrahydrocannabinol (THC) or cannabidiol (CBD) has been widely studied. However, the antinociceptive effects of other cannabis components, such as cannabichromene (CBC) and cannabigerol (CBG), have rarely been revealed. The antinociceptive mechanism of CBG is not yet clear, so we investigated the antinociceptive effect of CBG on different pain models, and explored the mechanism of action of CBG to exert antinociceptive effects. In the current study, we compared the antinociceptive effects of CBC, CBD, and CBG on the carrageenan-induced inflammatory pain model in mice, and the results showed that CBG had a better antinociceptive effects through intraplantar administration. On this basis, we further investigated the antinociceptive effect of CBG on CIA-induced arthritis pain model and nerve pain model in mice, and found that CBG also relieved on both types of pain. Then, we explored the antinociceptive mechanism of CBG, which revealed that CBG can activate TRPV1 and desensitize it to block the transmission of pain signals. In addition, CBG can further activate CB2R, but not CB1R, to stimulate the release of β-endorphin, which greatly promotes the antinociceptive effect. Finally, the safety test results showed that CBG had no irritating effect on the rabbits’ skin, and it did not induce significant biochemical and hematological changes in mice. Transdermal delivery results also indicated that CBG has certain transdermal properties. Overall, this study indicates that CBG is promising for developing a transdermal dosage for pain management.

The interplay between superconductivity and charge density wave (CDW) gives rise to exotic quantum phenomena. Here, the authors observe magnetoresistance oscillations and an anomalous metal state due to the coexistence of superconductivity and CDW in lithium intercalated TiSe2.

Abstract Tumor metastasis induced by drug resistance is a major challenge in successful cancer treatment. Nevertheless, the mechanisms underlying the pro-invasive and metastatic ability of drug resistance remain elusive. Exosome-mediated intercellular communications between cancer cells and stromal cells in tumor microenvironment are required for cancer initiation and progression. Recent reports have shown that communications between cancer cells also promote tumor aggression. However, little attention has been regarded on this aspect. Herein, we demonstrated that drug-resistant cell-derived exosomes promoted the invasion of sensitive breast cancer cells. Quantitative proteomic analysis showed that EphA2 was rich in exosomes from drug-resistant cells. Exosomal EphA2 conferred the invasive/metastatic phenotype transfer from drug-resistant cells to sensitive cells. Moreover, exosomal EphA2 activated ERK1/2 signaling through the ligand Ephrin A1-dependent reverse pathway rather than the forward pathway, thereby promoting breast cancer progression. Our findings indicate the key functional role of exosomal EphA2 in the transmission of aggressive phenotype between cancer cells that do not rely on direct cell–cell contact. Our study also suggests that the increase of EphA2 in drug-resistant cell-derived exosomes may be an important mechanism of chemotherapy/drug resistance-induced breast cancer progression.

HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited in vitro cell proliferation of multiple cancer cell lines and macrophages, and the in vivo anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The in vivo data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the in vitro anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and in vitro Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.

Myosin superfamily, a large and diverse family of molecular motors important for cell motility and migration, has been illustrated to play contradictory roles during the development of several kinds of tumors. However, the function and prognostic values of MYOs in head and neck squamous cell carcinoma (HNSCC) still remain largely unknown. In the current manuscript, the expression levels and clinical data of MYOs in HNSCC were investigated by online databases, including Oncomine, GEPIA, GEO, TCGA, HPA, UALCAN, Kaplan-Meier plotter, and CancerSEA; we found that the expression levels of MYO1B, MYO5A, and MYO10 were significantly elevated in HNSCC tissues, which were also correlated with the unfavorable overall survival (OS) of the patients. Furthermore, MYO1B/MYO5A/MYO10 interacting genes were identified, and the protein-protein interaction (PPI) networks were constructed by STRING and GeneMANIA. The enrichment analysis revealed that MYO1B/MYO5A/MYO10 associated genes mainly participated in cell metastasis and EMT processes, which were also confirmed by cell functional experiments. At last, the ssGSEA method was conducted to investigate the extent of immune cell infiltration, and we found that both the expression of MYO1B/MYO5A/MYO10 were closely correlated with the infiltration of immune cells in HNSCC. These findings implied that MYO1B, MYO5A, and MYO10 as novel prognostic factors for HNSCC and provided new strategy for HNSCC treatment.

Degradation of the antidepressant venlafaxine by an effective electrocatalytic process, boron-doped diamond (BDD) electrode, was study. The BDD electrode was selected as the anode, and the degradation efficiency of venlafaxine under different influencing factors was systematically investigated. The preliminary grasp of the degradation law of venlafaxine by anodic electro-degradation using BDD electrode was obtained. The experimental results showed that the electrochemical oxidation technology using BDD anode can effectively degrade venlafaxine and remove total organic carbon (TOC) from the solution, complete venlafaxine degradation and TOC elimination could be achieved within 30 and 120 min of BDD oxidation process, respectively, and it has good stability and reusability. Increasing the electrolyte concentration (≤0.1 mol/L) and current density (≤100 mA/cm2) within a certain range could accelerate the degradation of venlafaxine. HCO3– and PO43− could inhibit the degradation efficiency of venlafaxine through of competing for free radicals. It is interesting that the presence of Cl− significantly promoted the degradation efficiency of venlafaxine. The results of this study suggest that the Electro-degradation treatment may provide a promising way to treat venlafaxine contaminated water.

Modified Sijunzi Decoction (MSJZD) is an empirical prescription of Traditional Chinese Medicine (TCM) and has been corroborated to be effective in multiple human diseases, but its role in non-small cell lung cancer (NSCLC) is enigmatic. Here we mainly analyze the function and mechanism of MSJZD in NSCLC. In this study, we used a method that coupled ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to investigate the major constituents in MSJZD with positive and negative ion modes. Additionally, in in vitro experiments, the effects of serum-containing MSJZD on the biological behavior of NSCLC cells induced by TGF-β1 were assessed by cell function experiments. Then, the influences of serum-containing MSJZD on epithelial-mesenchymal transition (EMT)-related markers were examined by immunofluorescence and western blot assays. Also, the AKT/GSK3β pathway and apoptosis-related markers were estimated by western blotting. Tumor xenografts were generated by subcutaneously injecting A549 cells into BALB/c nude mice to determine the effects of MSJZD in vivo. We first analyzed the composition of MSJZD. In positive ion mode, 47 kinds of components were identified. In negative ion mode, 45 kinds of components were identified. We also found that TGF-β1 contributed to inducing cell morphological changes and EMT progression. In vitro, surprisingly, cell proliferation, migration as well as invasion in NSCLC cells induced by TGF-β1, could be weakened by serum-containing MSJZD, and apoptosis was intensified. Moreover, serum-containing MSJZD weakened EMT passage and AKT/GSK3β pathway activation and induced apoptosis-related markers in NSCLC cells triggered by TGF-β1. In vivo, we discovered that MSJZD attenuated the tumor growth, promoted histopathological damage, and induced apoptosis in A549 tumor-bearing mice. Importantly, MSJZD has also restrained the development of EMT, AKT/GSK3β pathway, and TGF-β1 expression levels in nude mice. These findings demonstrated that MSJZD significantly weakened NSCLC progression by modulating EMT and AKT/GSK3β pathway.

Eltrombopag is a small molecule TPO-R agonist that has been shown in our previous studies to inhibit tumor growth by targeting Human antigen R (HuR) protein. HuR protein not only regulates the mRNA stability of tumor growth-related genes, but it also regulates the mRNA stability of a variety of cancer metastasis-related genes, such as Snail, Cox-2, and Vegf-c. However, the role and mechanisms of eltrombopag in breast cancer metastasis have not been fully investigated. The purpose of this study was to investigate whether eltrombopag can inhibit breast cancer metastasis by targeting HuR. Our study first found that eltrombopag can destroy HuR-AU-rich element (ARE) complexes at the molecular level. Secondly, eltrombopag was found to suppress 4T1 cell migration and invasion and inhibit macrophage-mediated lymphangiogenesis at the cellular level. In addition, eltrombopag exerted inhibitory effects on lung and lymph node metastasis in animal tumor metastasis models. Finally, it was verified that eltrombopag inhibited the expressions of Snail, Cox-2, and Vegf-c in 4T1 cells and Vegf-c in RAW264.7 cells by targeting HuR. In conclusion, eltrombopag displayed antimetastatic activity in breast cancer in an HuR dependent manner, which may provide a novel application for eltrombopag, hinting at the multiple effects of HuR inhibitors in cancer therapy.

The Qinghai-Tibetan Plateau (QTP) is a global center of cold and dry, where the most extensive fragile alpine vegetation exists. Quantitative analysis of drought event characteristics and vegetation response to drought on the QTP is indispensable for understanding the increasing drought events in a warming climate which exacerbate adverse influence on extremely alpine ecosystems. Here, using the standardized precipitation evapotranspiration index (SPEI) and the normalized difference vegetation index (NDVI) from 2000 to 2018, this study analyzed the characteristics of drought events, their temporal impacts, and the stability of vegetation response to drought on the QTP. Results showed that: the characteristics of drought events on the QTP have clear spatial heterogeneity. When compared to the east monsoon region, most of the western regions have higher frequency and lower intensity of drought events. Drought has significant temporal effects on vegetation in grassland areas of the QTP during the growing season, which reach their peak in July and August. The 0–1-month and 3-month time scales were the optimal lagged and accumulated time during the growing season, respectively. The stability of vegetation response to drought showed significant spatial heterogeneity and varied with eco-geographical regions and vegetation types. Generally, forest areas showed high resistance (74.09) and resilience (2.26), followed by crop and grassland areas.

Clubroot disease is a kind of soil-borne disease that seriously infects Brassica species. In this study, we collected 121 varieties of non-heading Chinese cabbages. In order to better understand the genetic variation and to screen suitable clubroot disease-resistant parental material, we re-sequenced them to examine the population genetic structure, population genetic diversity, population differentiation index, and selective sweep based on SNPs. The mapping rate with the reference genome was high, and data quality analysis revealed that the sequencing quality was good. The annotated data indicated that intronic and intergenic areas held the majority of SNPs and indels. Four subgroups of 121 non-heading Chinese cabbages were identified using principal component analysis, phylogenetic tree, and genetic structure analysis. An examination of genetic diversity revealed that while selfing may happen in subgroups C and D, heterozygosity may exist in subgroups A and B. In subgroup B, self-fertilization is not possible. There was a moderate degree of genetic differentiation between subgroups B and C (Fst = 0.0744347). For genes in certain sweep regions, we also ran GO enrichment and KEGG enrichment analysis. Two disease resistance-related genes, BraA01g042910.3.5C and BraA06g019360.3.5C, were examined. These findings will serve as a theoretical foundation for developing novel, clubroot disease-resistant types of non-heading Chinese cabbages.

Recent evidence suggests that splicing factors (SFs) and alternative splicing (AS) play important roles in cancer progression. We constructed four SF-risk-models using 12 survival-related SFs. In Luminal-A, Luminal-B, Her-2, and Basal-Like BRCA, SF-risk-models for three genes (PAXBP1, NKAP, and NCBP2), four genes (RBM15B, PNN, ACIN1, and SRSF8), three genes (LSM3, SNRNP200, and SNU13), and three genes (SRPK3, PUF60, and PNN) were constructed. These models have a promising prognosis-predicting power. The co-expression and protein-protein interaction analysis suggest that the 12 SFs are highly functional-connected. Pathway analysis and gene set enrichment analysis suggests that the functional role of the selected 12 SFs is highly context-dependent among different BRCA subtypes. We further constructed four AS-risk-models with good prognosis predicting ability in four BRCA subtypes by integrating the four SF-risk-models and 21 survival-related AS-events. This study proposed that SFs and ASs were potential multidimensional biomarkers for the diagnosis, prognosis, and treatment of BRCA.

ATP-binding cassette (ABC) transporter family are major contributors to the drug resistance establishment of breast cancer cells. Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. However, recent studies suggest that the biological function of BCRP is not limited in its drug pump activity. Herein, the role of BCRP in the proliferation and survival of drug-resistant breast cancer cells was investigated. We found that BCRP is not the major drug pump to efflux epirubicin in the resistant cells that express multiple ABC transporters. Silencing of BCRP significantly impairs cell proliferation and induces apoptosis of the resistant cells in vitro and in vivo. RNA-sequencing and high-throughput proteomics suggest that BCRP is an inhibitory factor of oxidative phosphorylation (OXPHOS). Further research suggests that BCRP is localized in the mitochondria of the resistant cells. Knockdown of BCRP elevated the intracellular reactive oxygen species level and eventually promotes the cell to undergo apoptosis. This study demonstrated that BCRP exerts important onco-promoting functions in the drug-resistant breast cancer cells independent of its well-recognized drug efflux activity, which shed new light on understanding the complex functional role of ABC transporters in drug-resistant cells.

Abstract Clubroot, caused by Plasmodiophora Brassicae, is a serious soil-borne disease in worldwide. In recent years, progression of clubroot is rapid and serious in Shanghai, China. In this study, The inheritance of clubroot resistance (CR) were determined in pakchoi using F2 segregation population that were developed by crossing highly resistant line ‘CR38’ and susceptible line ‘CS22’. Two novel QTLs, qBrCR38-1 and qBrCR38-2, was identified by BSA-seq (Bulked Segregant Sequencing) resistant to P. brassicae physiological race 7. Two significant peak qBrCR38-1 and qBrCR38-2 were observed by three statistical methods between interval of 19.7–20.6 Mb in chromosome A07 and 20.0–20.6 Mb in chromosome A08, respectively. In addition, Polymorphic SNPs identified within target regions were converted to kompetitive allele-specific PCR (KASP) assays. In target regions of qBrCR38-1 and qBrCR38-2, there were twenty SNP sites identified, eleven KASP markers of which are significantly associated to CR (P

Background: Arugula is an essential oil crop of cruciferous species worldwide and serves as a salad vegetable. Purple plant leaves provide nutrients benefiting human beings and are mainly attributed to high anthocyanins. In this study, we collected a purple arugula cultivar with purple leaves and a green arugula with green leaves. The genetic bases and mechanisms underlying purple leaf formation in arugula remain unclear. Therefore, we conducted integrative metabolomics and transcriptomics of two arugula cultivars with different leaf colors. Methods: To study the underlying mechanisms, transcriptomic and metabolomic analyses were carried out. Results: Metabolomic analysis revealed that 84 of 747 metabolites were significantly differentially expressed, comprising 30 depleted and 49 enriched metabolites. Further analysis showed that cyanidin is the main components responsible for the purple color. A total of 144,790 unigenes were obtained by transcriptomic analysis, with 13,204 unigenes differentially expressed, comprising 8120 downregulated and 5084 upregulated unigenes. Seven structural genes, PAL, C4H, 4CL, CHS, CCoAOMT, LDOX, and UFGT, were identified as candidate genes associated with anthocyanin accumulation through combined analysis of transcriptome and metabolome. Conclusions: Collectively, the differences in the expression levels of PAL, C4H, 4CL, CHS, CCoAOMT, LDOX, and UFGT might be responsible for purple leaf coloration, providing important data for the discovery of candidate genes and molecular bases controlling the purple leaves in arugula.

As a novel interfacial high-temperature superconductor, monolayer FeSe on SrTiO3 has been intensely studied in the past decade. The high selenium flux involved in the traditional growth method complicates the film’s composition and entails more sample processing to realize the superconductivity. Here we use a Se cracking source for the molecular beam epitaxy growth of FeSe films to boost the reactivity of the Se flux. Reflection high-energy electron diffraction shows that the growth rate of FeSe increases with the increasing Se flux when the Fe flux is fixed, indicating that the Se over-flux induces Fe vacancies. Through careful tuning, we find that the proper Se/Fe flux ratio with Se cracked that is required for growing stoichiometric FeSe is close to 1, much lower than that with the uncracked Se flux. Furthermore, the FeSe film produced by the optimized conditions shows high-temperature superconductivity in the transport measurements without any post-growth treatment. Our work reinforces the importance of stoichiometry for superconductivity and establishes a simpler and more efficient approach to fabricating monolayer FeSe superconducting films.

Clubroot is one of the most serious diseases affecting Brassicaceae plants worldwide. However, there is no effective control method for clubroot. Salicylic acid (SA) is a plant hormone that plays a critical role in plant defense. In our study, we found the disease severity of a clubroot-sensitive cultivar of pakchoi, Xinxiaqing, was reduced with 0.6mM exogenous SA after the infection of P. brassicae. To investigate the mechanism of SA-reduced disease severity against clubroot, then we analyzed the plant growth, alteration of antioxidant enzyme system, and related gene expression of Xinxiaqing. Results showed that the clubroot incidence rate and disease index were decreased after being treated with 0.6 mM exogenous SA. Furthermore, plant growth, reactive oxygen species (ROS) contents, and membrane lipid peroxidation were changed. The activities of antioxidant enzymes, including superoxide dismutase (SOD), ascorbic acid-peroxidase (APX), catalase (CAT), and glutathione reductase (GR), were increased. Additionally, the production rates of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2·-) were also inhibited. The expression levels of genes, encoding SOD, APX, CAT, and GR, were increased. By summering all results, we conclude that 0.6 mM SA contributes to the reduction of disease severity to clubroot by increasing the activities of antioxidant enzymes, abilities of osmotic regulation, and ROS scavenging to reduce the clubroot-induced damage in pakchoi.

A large-scale persistent strong dense fog (SDF) event that occurred from December 30, 2016, to January 5, 2017, in central and eastern China is analyzed by using a variety of data, including high-resolution satellite and surface observations, meteorological tower observations, fine-resolution sounding observations, and NCEP/NCAR reanalysis data. The results show the following: (1) The SDF event has the characteristics of long duration, wide influence range, large intensity, and serious air pollution. During the study period, there are 531 stations with SDF events, covering an area of over 360,000 km2. There were five stations in Hebei province where the fog lasted for more than 77 hours, and even some stations did not dissipate during the day. (2) Radiation fog and advection fog alternate in this SDF event, namely, radiation fog (20:00 BT on December 30 to 14:00 on January 1), advection radiation fog (20:00 on January 1 to 08:00 on January 2), radiation fog (night on January 2 to daytime on January 3), and advection radiation fog (night on January 3 to January 5). The characteristic of radiation fog is that the central and eastern part of China was controlled by “L” type high pressure. In the stage of advection radiation fog, the combined effect of weak cold advection and radiation cooling leads to the occurrence of SDF. (3) Regarding the duration of the fog event, the inversion structure is continuously maintained at night and in the morning near the stratum, and when the fog intensity is strong, the inversion intensity is correspondingly large, the fog top is lower than the inversion layer top, and the top of the SDF is between 80 and 400 meters.

Objective: To study the efficacy of Professor Zhiqiang Guo's unique sequential herbal therapy in the treatment of premature ovarian insufficiency (POI) of the kidney deficiency and liver constraint pattern. Methods: Ninety patients with POI who consulted with Professor Guo at Dongzimen Hospital, Beijing University of Chinese Medicine from January 2012 to December 2015 were enrolled. Treatment consisted of sequential therapy using traditional Chinese medicine formulae with the actions of nourishing the liver and kidney. Course of treatment was 3 consecutive menstrual cycles for each participant except for those who became pregnant during treatment. Baseline data including age, course of disease, past medical history, lifestyle, pregnancy outcome, menstrual status (cycle length, menstrual flow duration and volume), as well as gonadal hormone levels before and after treatment were recorded and analyzed. Results: During treatment, 18 (20.0%) participants became pregnant. Symptoms including scanty menstrual flow, irritability, low libido, insomnia and excessive dreaming at night, nightsweats, hot flashes, and depression were markedly alleviated. Changes in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at early follicular stage were observed (P = .009 and P = .002, respectively), and FSH/LH differed significantly pre- and posttreatment (P = .044). Conclusion: Professor Guo's sequential Chinese herbal therapy with the actions of nourishing the liver and kidney to treat POI can enhance ovarian function, promote pregnancy, and improve quality of life. Keywords: Premature ovarian insufficiency, Infertility, Traditional Chinese herbal medicinals, Sequential therapy, Nourish the liver and kidney

Since the discovery of high-temperature superconductivity in cuprates, Josephson junction based phase-sensitive experiments are believed and used to provide the most convincing evidence for determining the pairing symmetry. Regardless of different junction materials and geometries used, quantum tunneling involved in these experiments is essentially a nanoscale process, and thus, actual experimental results are extremely sensitive to atomic details of the junction structures. The situation has led to controversial results as to the nature of the pairing symmetry of cuprates: while in-plane junction experiments generally support d-wave pairing symmetry, those based on out-of-plane (c-axis) Josephson junctions between two rotated cuprate blocks favor s-wave pairing. In this work, we revisit the c-axis experiment by fabricating Josephson junctions with atomic-level control in their interface structure. We fabricate over 90 junctions of ultrathin Bi_{2}Sr_{2}CaCu_{2}O_{8+x} (BSCCO) flakes by state-of-the-art exfoliation technique and obtain atomically flat junction interfaces in the whole junction regions as characterized by high-resolution transmission electron microscopy. Notably, the resultant uniform junctions at various twist angles all exhibit a single tunneling branch behavior, suggesting that only the first half of a unit cell on both sides of the twisted flakes is involved in the Josephson tunneling process. With such well-defined geometry and structure and the characteristic single tunneling branch, we repeatedly observe Josephson tunneling at a nominal twist angle of 45°, which is against the expectation from a purely d-wave pairing scenario. Our results strongly favor the scenario of a persistent s-wave order parameter in the junction.

The biotrophic protist Plasmodiophora brassicae causes serious damage to Brassicaceae crops grown worldwide. However, the molecular mechanism of the Brassica rapa response remains has not been determined. Long noncoding RNA and mRNA expression profiles in response to Plasmodiophora brassicae infection were investigated using RNA-seq on the Chinese cabbage inbred line C22 infected with P. brassicae. Approximately 5,193 mRNAs were significantly differentially expressed, among which 1,345 were upregulated and 3,848 were downregulated. The GO enrichment analysis shows that most of these mRNAs are related to the defense response. Meanwhile, 114 significantly differentially expressed lncRNAs were identified, including 31 upregulated and 83 downregulated. Furthermore, a total of 2,344 interaction relationships were detected between 1,725 mRNAs and 103 lncRNAs with a correlation coefficient greater than 0.8. We also found 15 P. brassicaerelated mRNAs and 16 lncRNA interactions within the correlation network. The functional annotation showed that 15 mRNAs belong to defense response proteins (66.67%), protein phosphorylation (13.33%), root hair cell differentiation (13.33%) and regulation of salicylic acid biosynthetic process (6.67%). KEGG annotation showed that the vast majority of these genes are involved in the biosynthesis of secondary metabolism pathways and plant-pathogen interactions. These results provide a new perspective on lncRNA-mRNA network function and help to elucidate the molecular mechanism of P. brassicae infection.

In recent years, the interest in radar automatic target recognition (RATR) based on the carrier-free ultra-wideband (UWB) radar has been increasing. Compared with narrow-band and other bandwidth radars, the echo signal of the carrier-free UWB radar includes more comprehensive and detailed information with respect to the targeted object. In this paper, we first utilized 3ds Max to acquire accurate geometric models and applied a time-domain integral equation (TDIE) for echo signal acquisition under the condition that the transmitted signals had an extremely short duration period. By comparing the simulated waveform with the actual one, the accuracy of the electromagnetic modeling is verified. Furthermore, given that the actual environment is full of noise and clutter, we propose an improved two-dimensional variational mode decomposition (2D-IVMD), and an algorithm is proposed to eliminate noise and extract edge features preliminarily, which lays a foundation for further in-depth feature extraction. Then, the deep conventional neural network (DCNN) is introduced for the final recognition. The results show that the proposed methods achieve promising classification performance under the condition of low signal-to-noise ratio (SNR) values.

In the early December 2013, dense fog involving heavy pollutants lasted for 9 days in the Yancheng area. The characteristics, formation, and lasting mechanisms of this persistent fog were analyzed based on observational data at the Sheyang site, reanalysis data, and final analysis data from NCEP/NCAR, combining with the weather background and meteorological and physical variable fields. Results include that (1) the fog process was characterized by long duration, low visibility, and high pollutants concentration, (2) the atmospheric general circulation contributed to the sustainability and development of the heavily polluted fog, (3) deep inversion was the key thermal factor causing the heavily polluted fog, (4) the fog exhibited obvious outbreaks with good visibility weather turned to severe fog several times, and (5) the weak cold air invasion and radiative cooling were the triggering factors to the sudden enhancement of the fog.

Viruses are intracellular obligate parasites and the host cellular machinery is usually recruited for their replication. Human eukaryotic translation initiation factor 3 (eIF3) could be directly recruited by the hepatitis C virus (HCV) internal ribosome entry site (IRES) to promote the translation of viral proteins. In this study, we establish a fluorescence polarization (FP) based high throughput screening (HTS) system targeting the interaction between HCV IRES and eIF3. By screening a total of 894 compounds with this HTS system, two compounds (Mucl39526 and NP39) are found to disturb the interaction between HCV IRES and eIF3. And these two compounds are further demonstrated to inhibit the HCV IRES-dependent translation in vitro. Thus, this HTS system is functional to screen the potential HCV replication inhibitors targeting human eIF3, which is helpful to overcome the problem of viral resistance. Surprisingly, one compound HP-3, a kind of oxytocin antagonist, is discovered to significantly enhance the interaction between HCV IRES and eIF3 by this HTS system. HP-3 is demonstrated to directly interact with HCV IRES and promote the HCV IRES-dependent translation both in vitro and in vivo, which strongly suggests that HP-3 has potentials to promote HCV replication. Therefore, this HTS system is also useful to screen the potential HCV replication enhancers, which is meaningful for understanding the viral replication and screening novel antiviral drugs. To our knowledge, this is the first HTS system targeting the interaction between eIF3 and HCV IRES, which could be applied to screen both potential HCV replication inhibitors and enhancers.

Anthocyanins are secondary metabolites that contribute to red, blue, and purple colors in plants and are affected by light, but the effects of low light on the physiological responses of purple pak-choi plant leaves are still unclear. In this study, purple pak-choi seedlings were exposed to low light by shading with white gauze and black shading in a phytotron. The responses in terms of photosynthetic properties, carbohydrate metabolism, antioxidant enzyme activity, anthocyanin biosynthetic enzyme activity, and the relative chlorophyll and anthocyanin content of leaves were measured. The results showed that chlorophyll b, intracellular CO2 content, stomatal conductance and antioxidant activities of guaiacol peroxidase, catalase and superoxide dismutase transiently increased in the shade treatments at 5 d. The malondialdehyde content also increased under low light stress, which damages plant cells. With the extension of shading time (at 15 d), the relative chlorophyll a, anthocyanin and soluble protein contents, net photosynthetic rate, transpiration rate, stomata conductance, antioxidant enzyme activities, and activities of four anthocyanin biosynthetic enzymes decreased significantly. Thus, at the early stage of low light treatment, the chlorophyll b content increased to improve photosynthesis. When the low light treatment was extended, antioxidant enzyme activity and the activity of anthocyanin biosynthesis enzymes were inhibited, causing the purple pak-choi seedlings to fade from purple to green. This study provides valuable information for further deciphering genetic mechanisms and improving agronomic traits in purple pak-choi under optimal light requirements.