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Abstract Epistasis is one of important genetic components for a quantitative trait in plant. Eshed and Zamir found negative epistatic interactions of quantitative trait loci in Tomato first. We detected that positive (negative) QTLs generated mostly negative (positive) epistatic interactions on heading date in rice, and then proposed the hypothese that QTL epistasis plays a role of homeostasis in one of our recent papers. In order to further provide additional evidence, the effects of QTLs and their epistatic effects on two quantitative traits of plant height (ph) and thousand kernel weight (tkw) were analyzed in this study. The same regularity was verified again. We detected that positive ph QTLs and negative tkw QTLs always generated reverse epistatic effects, respectively. Moreover, high-order epistatic effects were estimated on these two traits. The sum of all epistatic effects would partially neutralize the additive of constitutive QTL effects. This feature of epistsis would be the mechanism for bionts to maintain homeostasis while the obstacle for human to achieve the pyramiding breeding objectives. More evidences are still being collected to support our assumption.

Abstract Cation exchanger (CAX) genes play an important role in plant growth/development and response to biotic and abiotic stresses. Here, we tried to obtain important information on the functionalities and phenotypic effects of CAX gene family by systematic analyses of their expression patterns, genetic diversity (gene CDS haplotypes, structural variations, gene presence/absence variations) in 3010 rice genomes and nine parents of 496 Huanghuazhan introgression lines, the frequency shifts of the predominant gcHaps at these loci to artificial selection during modern breeding, and their association with tolerances to several abiotic stresses. Significant amounts of variation also exist in the cis-regulatory elements (CREs) of the OsCAX gene promoters in 50 high-quality rice genomes. The functional differentiation of OsCAX gene family were reflected primarily by their tissue and development specific expression patterns and in varied responses to different treatments, by unique sets of CREs in their promoters and their associations with specific agronomic traits/abiotic stress tolerances. Our results indicated that OsCAX1a and OsCAX2 as general signal transporters were in many processes of rice growth/development and responses to diverse environments, but they might be of less value in rice improvement. OsCAX1b, OsCAX1c, OsCAX3 and OsCAX4 was expected to be of potential value in rice improvement because of their associations with specific traits, responsiveness to specific abiotic stresses or phytohormones, and relatively high gcHap and CRE diversity. Our strategy was demonstrated to be highly efficient to obtain important genetic information on genes/alleles of specific gene family and can be used to systematically characterize the other rice gene families.

Abstract Background WD40 proteins, which are highly prevalent in eukaryotes, play important roles in plant development and stress responses. However, systematic identification and exploration of WD40 proteins in tobacco have not yet been conducted. Results In this study, a total of 399 WD40 regulatory genes were identified in common tobacco (Nicotiana tabacum). Gene structure and motif analysis revealed structural and functional diversity among different clades of tobacco WD40 regulatory genes. The expansion of tobacco WD40 regulatory genes was mainly driven by segmental duplication and purifying selection. A potential regulatory network of NtWD40s suggested that NtWD40s might be regulated by miRNAs and transcription factors in various biological processes. Expression pattern analysis via transcriptome analysis and qRT-PCR revealed that many NtWD40s exhibited tissue-specific expression patterns and might be involved in various biotic and abiotic stresses. Furthermore, we have validated the critical role of NtTTG1, which was located in the nuclei of trichome cells, in enhancing the drought tolerance of tobacco plants. Conclusions Our study provides comprehensive information to better understand the evolution of WD40 regulatory genes and their roles in different stress responses in tobacco.

Abstract Background N 6-methyladenosine (m6A) is one of the common internal RNA modifications found in eukaryotes. The m6A modification can regulate various biological processes in organisms through the modulation of alternative splicing, alternative polyadenylation, folding, translation, localization, transport, and decay of multiple types of RNA, without altering the nucleotide sequence. The three components involved in m6A modification, namely writer, eraser, and reader, mediate the abundance of RNA m6A modification through complex collaborative actions. Currently, research on m6A regulatory genes in plants is still in its infancy. Results In this study, we identified 52 candidate m6A regulatory genes in common tobacco (Nicotiana tabacum L.). Gene structure, conserved domains, and motif analysis showed structural and functional diversity among different subgroups of tobacco m6A regulatory genes. The amplification of m6A regulatory genes were mainly driven by polyploidization and dispersed duplication, and duplicated genes evolved through purified selection. Based on the potential regulatory network and expression pattern analysis of m6A regulatory genes, a significant number of m6A regulatory genes might play important roles in growth, development, and stress response processes. Furthermore, we have confirmed the critical role of NtFIP37B, an m6A writer gene in tobacco, in enhancing drought resistance. Conclusions This study provides useful information for better understanding the evolution of m6A regulatory genes and the role of m6A modification in tobacco stress response, and lays the foundation for further elucidating the function of m6A regulatory genes in tobacco.

Abstract Background The remarkable regenerative capacity of the liver enables recovery after radical Hepatocellular carcinoma (HCC) resection. After resection, macrophages secrete interleukin 6 and hepatocyte growth factors to promote liver regeneration. Ten-eleven translocation-2 (Tet2) DNA dioxygenase regulates pro-inflammatory factor secretion in macrophages. In this study, we explored the role of Tet2 in macrophages and its function independent of its enzymatic activity in liver regeneration. Methods The model of liver regeneration after 70% partial hepatectomy (PHx) is a classic universal model for studying reparative processes in the liver. Mice were euthanized at 0, 24, and 48 h after PHx. Enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, immunofluorescence analysis, and flow cytometry were performed to explore immune cell infiltration and liver regenerative capability. Molecular dynamics simulations were performed to study the interaction between Tet2 and signal transducer and activator of transcription 1 (Stat1). Results Tet2 in macrophages negatively regulated liver regeneration in the partial hepatectomy mice model. Tet2 interacted with Stat1, inhibiting the expression of proinflammatory factors and suppressing liver regeneration. The Tet2 inhibitor attenuated the interaction between Stat1 and Tet2, enhanced Stat1 phosphorylation, and promoted hepatocyte proliferation. The proliferative function of the Tet2 inhibitor relied on macrophages and did not affect hepatocytes directly. Conclusion Our findings underscore that Tet2 in macrophages negatively regulates liver regeneration by interacting with Stat1. Targeting Tet2 in macrophages promotes liver regeneration and function after a hepatectomy, presenting a novel target to promote liver regeneration and function. Graphical Abstract Tet2 interacts with Stat1 in the cytoplasm and suppresses IFN-γ-induced macrophage activation. Tet2 inhibitor decreases the combination of Stat1 and Tet2, activating the macrophages through the Jak-Stat pathway. The activation of macrophages increases the transcription and translation of the IL-6 and promotes liver regeneration. Video Abstract

Abstract Background Arthritis primarily affects older people and is a prominent cause of their activity impairment. This study aimed to examine the mediating role of depressive symptoms in the relationship between social participation and activity impairment, as well as to determine whether sex moderated the mediating effect. Methods A total of 2247 older patients with arthritis were included from the China Health and Retirement Longitudinal Study between 2015 and 2018. We first examined a simple mediation model where depressive symptoms were a mediator between social participation and activity impairment. Furthermore, sex was systematically integrated into the model as a moderator. The mediation model and moderated mediation model were analyzed using PROCESS macro. Results Mediation analysis revealed that the association between social participation and activity impairment was partially mediated by depressive symptoms (B = -0.10, 95% CI = [-0.14, -0.06]) with intermediary effect of 28.6%. Moderated mediation analysis indicated that mediation model was moderated by sex. The indirect effect of social participation on activity impairment among female patients (B = -0.15, 95% CI = [-0.21, -0.09]) was stronger than male patients (B = -0.04, 95% CI = [-0.09, -0.01]). Conclusion Social participation was the key protective factor associated with depressive symptoms and activity impairment among arthritis patients. Encouraging arthritis patients to social participation and improving the depressive symptoms might avoid activity impairment, especially for female patients.

Abstract If there was no gene interaction, the gene aggregation effect would increase infinitely with the increase of gene number. Epistasis avoids the endless accumulation of gene effects, playing a role of homeostasis. To confirm the role, QTL epistases were analyzed by four single-segment substitution lines with heading date QTLs in this paper. We found that QTLs of three positive effects and one negative effect generated 62.5% negative dual QTL epistatic effects and 57.7% positive triple QTL epistatic effects, forming the relationship “positive QTLs-negative one order interactions-positive two order interactions”. In this way, the aggregation effect of QTLs was partially neutralized by the opposite epistatic effect sum. There also were two exceptions, QTL OsMADS50 and gene Hd3a-2 were always with consistent effect directions with their epistases, implying they could be employed in pyramiding breeding with different objectives. This study elucidated the mechanism of epistatic interactions among four QTLs and provided valuable genetic resources for improving heading date in rice.

Abstract Carbon nanosol (CNS) is a carbon-based nanomaterial that promotes plant growth; however, its functional mechanisms and effects on the microbiome are not fully understood. Here, we explored the effects of CNS on the relationship between the soil, endophytic microbiomes and plant productivity. CNS treatment increased the fresh biomass of tobacco (Nicotiana tabacum L.) plants by 27.4% ± 9.9%. Amplicon sequencing analysis showed that the CNS treatment significantly affected the composition and diversity of the microbial communities in multiple ecological niches associated with tobacco, especially the bulk soil and stem endophytic microbiome. Furthermore, the application of CNS resulted in enhanced network connectivity and stability of the microbial communities in different niches, particularly in the soil, implying a strengthening of certain microbial interactions. Certain potentially growth-promoting root endophytic bacteria were more abundant under the CNS treatment. In addition, CNS increased the abundance of some endophytic microbial functional genes known to enhance plant growth, such as those associated with nutrient metabolism and the plant hormone biosynthesis pathways. We isolated two bacterial strains (Sphingopyxis sp. and Novosphingobium sp.) that were enriched under CNS treatment, and they were confirmed to promote tobacco plant growth in vitro. These results suggested that CNS might, at least in part, promote plant growth by enriching beneficial bacteria in the microbiome. Graphical Abstract

Patrinia scabiosaefolia, is used as wild vegetable in China for more than 2 000 years, with a variety of pharmacological activities, including anti-inflammatory, anti-tumor and hypoglycemic. Based on our ongoing research on chemical constituents and hypoglycemic activity of P. scabiosaefolia, 4 lignan compounds, (+)-isolariciresinol (1), 7R,7'R,8S,8'S-(+)-neo-olivil-4-O-β-D-glucopyranoside (2), 4-O-methylcedrusin (3) and patrinian A (4), were isolated and identified. The hypoglycemic activity showed that compounds 2 and 3 could extremely significantly improve insulin resistance at 100 (P < 0.001), 50 (P < 0.001) and 25 µmol/L (P < 0.01) in IR 3T3-L1 cells. While compound 4 only promoted glucose uptake by IR 3T3-L1 cells at 100 µmol/L (P < 0.01). Western blotting experiments showed that compounds 2 and 4 up-regulated the protein expressions of p-IRS, PI-3K, p-AKT and glucose transporter 4 (GLUT4), and promoted the transcription of GLUT4 mRNA. Therefore, the mechanisms of compounds 2 and 4 were presumed to improve IR by activating PI-3K/AKT signaling pathway.

Abstract Recent studies suggest that circular RNA (circRNA)‐mediated post‐translational modification of RNA‐binding proteins (RBP) plays a pivotal role in metastasis of hepatocellular carcinoma (HCC). However, the specific mechanism and potential clinical therapeutic significance remain vague. This study attempts to profile the regulatory networks of circRNA and RBP using a multi‐omics approach. Has_circ_0006646 (circ0006646) is an unreported circRNA in HCC and is associated with a poor prognosis. Silencing of circ0006646 significantly hinders metastasis in vivo. Mechanistically, circ0006646 prevents the interaction between nucleolin (NCL) and the E3 ligase tripartite motif‐containing 21 to reduce the proteasome‐mediated degradation of NCL via K48‐linked polyubiquitylation. Furthermore, the change of NCL expression is proven to affect the phosphorylation levels of multiple proteins and inhibit p53 translation. Moreover, patient‐derived tumor xenograft and lentivirus injection, which is conducted to simulate clinical treatment confirmed the potential therapeutic value. Overall, this study describes the integrated multi‐omics landscape of circRNA‐mediated NCL ubiquitination degradation in HCC metastasis and provides a novel therapeutic target.

To measure vibration signals, a low-frequency fiber Bragg grating (FBG) acceleration sensor featuring a flexible hinge with a spring support and symmetric compensation structure has been designed. Based on the mechanical model of the sensor’s structure, the expressions for sensitivity and resonant frequency of the sensor are derived. The structural parameters of the sensor are optimized, and a simulation analysis is conducted using ANSYS 19.2 software. According to the results of simulation analysis and size optimization, the sensor prototype is constructed. Subsequently, its amplitude-frequency response, sensitivity, and temperature characteristics are investigated through vibration experiments. The experimental results show that the resonant frequency of the sensor is 73 Hz, the operating frequency range is 0~60 Hz, and the sensitivity measures 24.24 pm/g. This design meets the requirements for measuring vibration signals at low frequencies.

Flower plants are popular all over the world and important sources of ornamental plants, bioactive molecules and nutrients. Flowers have a wide range of biological activities and beneficial pharmacological effects. Flowers and their active ingredients are becoming more and more popular in the preparation of food, drugs and industrial products. This paper summarizes the active ingredients, pharmacological activities and applications in the pharmaceutical and food industries of flower plants in recent years. In addition, the possible molecular mechanism of pharmacological effects of flower plants were also discussed. 302 active constituents from 55 species of flower plants were summarized, including flavonoids (115), terpenoids (90), phenylpropanoids (20), alkaloids (13), organic acids (27) and others (37). The pharmacological effects of flower plants are very extensive, mainly including antioxidant, anti-inflammatory, anti-tumor, anti-virus, and hypoglycemic. The mechanisms of anti-inflammatory, anti-tumor and hypoglycemic activities present the characteristics of multi-way and multi-target. Because of its rich nutrients, bioactive ingredients and plant essential oils, and its wide sources, flower plants are widely used in food, beverage, cosmetics and drug research. Flower plants also play an important role in pharmaceutical industry, food industry and other fields.

Abstract The multi-environment genomic selection enables plant breeders to select varieties resilient to diverse environments or particularly adapted to specific environments, which holds a great potential to be used in rice breeding. To realize the multi-environment genomic selection, a robust training set with multi-environment phenotypic data is of necessity. Considering the huge potential of genomic prediction enhanced sparse phenotyping on the cost saving of multi-environment trials (MET), the establishment of a multi-environment training set could also benefit from it. Optimizing the genomic prediction methods is also crucial to enhance the multi-environment genomic selection. Using haplotype-based genomic prediction models is able to capture local epistatic effects which could be conserved and accumulated across generations much like additive effects thereby benefitting breeding. However, previous studies often used fixed length haplotypes composed by a few adjacent molecular markers disregarding the linkage disequilibrium (LD) which is of essential role in determining the haplotype length. In our study, based on three rice populations with different sizes and compositions, we investigated the usefulness and effectiveness of multi-environment training sets with varying phenotyping intensities and different haplotype-based genomic prediction models based on LD-derived haplotype blocks for two agronomic traits, i.e., days to heading (DTH) and plant height (PH). Results showed that phenotyping merely 30% records in multi-environment training set is able to provide a comparable prediction accuracy to high phenotyping intensities; the local epistatic effects are much likely existent in DTH; dividing the LD-derived haplotype blocks into small segments with two or three single nucleotide polymorphisms (SNPs) helps to maintain the predictive ability of haplotype-based models in large populations; modelling the covariances between environments improves genomic prediction accuracy. Our study provides means to improve the efficiency of multi-environment genomic selection in rice.

Salinity is a major factor limiting rice productivity, and developing salt-tolerant (ST) varieties is the most efficient approach. Seventy-eight ST introgression lines (ILs), including nine promising lines with improved ST and yield potential (YP), were developed from four BC2F4 populations from inter-subspecific crosses between an elite Geng (japonica) recipient and four Xian (indica) donors at the Institute of Crop Sciences, Chinese Academy of Agricultural Sciences. Genome-wide characterization of donor introgression identified 35 ST QTLs, 25 of which harbor 38 cloned ST genes as the most likely QTL candidates. Thirty-four are Xian-Geng differentiated ones with the donor (Xian) alleles associated with ST, suggesting differentiated responses to salt stress were one of the major phenotypic differences between the two subspecies. At least eight ST QTLs and many others affecting yield traits were identified under salt/non-stress conditions. Our results indicated that the Xian gene pool contains rich ‘hidden’ genetic variation for developing superior Geng varieties with improved ST and YP, which could be efficiently exploited by selective introgression. The developed ST ILs and their genetic information on the donor alleles for ST and yield traits would provide a useful platform for developing superior ST and high-yield Geng varieties through breeding by design in the future.

Abstract Background Resveratrol is a commercially available stilbenoid widely used as dietary supplements, functional food ingredients, and cosmetic ingredients due to its diverse physiological activities. The production of resveratrol in microorganisms provides an ideal source that reduces the cost of resveratrol, but the titer in Saccharomyces cerevisiae was still much lower than that in other hosts. Results To achieve enhanced production of resveratrol in S. cerevisiae, we constructed a biosynthetic pathway via combining phenylalanine and tyrosine pathways by introducing a bi-functional phenylalanine/tyrosine ammonia lyase from Rhodotorula toruloides. The combination of phenylalanine pathway with tyrosine pathway led to a 462% improvement of resveratrol production in yeast extract peptone dextrose (YPD) medium with 4% glucose, suggesting an alternative strategy for producing p-coumaric acid-derived compounds. Then the strains were further modified by integrating multi-copy biosynthetic pathway genes, improving metabolic flux to aromatic amino acids and malonyl-CoA, and deleting by-pathway genes, which resulted in 1155.0 mg/L resveratrol in shake flasks when cultured in YPD medium. Finally, a non-auxotrophic strain was tailored for resveratrol production in minimal medium without exogenous amino acid addition, and the highest resveratrol titer (4.1 g/L) ever reported was achieved in S. cerevisiae to our knowledge. Conclusions This study demonstrates the advantage of employing a bi-functional phenylalanine/tyrosine ammonia lyase in the biosynthetic pathway of resveratrol, suggesting an effective alternative in the production of p-coumaric acid-derived compounds. Moreover, the enhanced production of resveratrol in S. cerevisiae lays a foundation for constructing cell factories for various stilbenoids. Graphical Abstract

Background Hemorrhagic cystitis (HC) is a severe complication of allo-HSCT, characterized by irritative symptoms of the urinary tract and a higher morbidity rate. The risk factors and prognosis of HC are still unclear.Objective The objective of this study is to identify risk factors and outcomes to improve treatment in pediatric SAA patients undergoing HSCTs in the Children's Hospital of Soochow University.Methods A total of 97 SAA patients as a cohort were enrolled from 2010 to 2019 in the Children's Hospital of Soochow University and a number of factors related to HC and outcomes were analysed. In all transplants (except UCBT), patients received a combination of G-CSF stimulated bone marrow (BM) and peripheral blood stem cell (PBSC). The minimum number of CD34 + cells is 5 × 106 cells/kg.Results Mononuclear cells dose (MNC, cut off: 8.53 × 108/kg) and grade II–IV acute graft versus host disease (aGVHD) were identified as independent risk factors for HC. Patients without HC had better overall survival (OS) than with HC (No HC: 98.6%±1.4% vs HC: 87.4% ± 6.8%, p = 0.03).Conclusion We concluded that aGVHD and MNC dose in graft might play an important role in the development of HC in pediatric SAA patients undergoing allo-HSCT. HC is also a key complication affecting the prognosis of children with SAA after allo-HSCT.

Abstract Background Ginsenosides are Panax plant-derived triterpenoid with wide applications in cardiovascular protection and immunity-boosting. However, the saponins content of Panax plants is fairly low, making it time-consuming and unsustainable by direct extraction. Protopanaxadiol (PPD) is a common precursor of dammarane-type saponins, and its sufficient supply is necessary for the efficient synthesis of ginsenoside. Results In this study, a combinational strategy was used for the construction of an efficient yeast cell factory for PPD production. Firstly, a PPD-producing strain was successfully constructed by modular engineering in Saccharomyces cerevisiae BY4742 at the multi-copy sites. Then, the INO2 gene, encoding a transcriptional activator of the phospholipid biosynthesis, was fine-tuned to promote the endoplasmic reticulum (ER) proliferation and improve the catalytic efficiency of ER-localized enzymes. To increase the metabolic flux of PPD, dynamic control, based on a carbon-source regulated promoter P HXT1 , was introduced to repress the competition of sterols. Furthermore, the global transcription factor UPC2-1 was introduced to sterol homeostasis and up-regulate the MVA pathway, and the resulting strain BY-V achieved a PPD production of 78.13 ± 0.38 mg/g DCW (563.60 ± 1.65 mg/L). Finally, sugarcane molasses was used as an inexpensive substrate for the first time in PPD synthesis. The PPD titers reached 1.55 ± 0.02 and 15.88 ± 0.65 g/L in shake flasks and a 5-L bioreactor, respectively. To the best of our knowledge, these results were new records on PPD production. Conclusion The high-level of PPD production in this study and the successful comprehensive utilization of low-cost carbon source -sugarcane molassesindicate that the constructed yeast cell factory is an excellent candidate strain for the production of high-value-added PPD and its derivativeswith great industrial potential. Graphical Abstract

To explore the influence of eccentricity errors on the dynamic characteristics of gear transmissions，a six-degree-of-freedom bending-torsional coupling vibration model of a spur gear pair with eccentricity error excitations is established by using the dynamics software Adams. The gear meshing stiffness and bearing support stiffness are theoretically calculated，and the numerical solution characterizing the meshing behavior and dynamic response of the system is obtained by GSTIFF integration method. The results show that the meshing related parameters such as gear pair center distance，meshing angle，contact ratio，backlash，transmission error and transmission ratio show time-varying characteristics under the influence of eccentricity errors，which increases the amplitude of vibration and dynamic loads of the gear system. And the modulation phenomenon appears with a series of sidebands related to eccentricity errors appearing near the meshing frequency. In addition，the existence of eccentricity errors changes the system vibration status，and makes the system vibration alter from single periodic response to quasi periodic response.

BackgroundGiven the continuing challenges frailty poses among people living with human immunodeficiency virus (HIV) (PLHIV), accumulating evidence suggests that frailty is linked to psychological factors. However, the mutual influences of resilience, depression, and frailty have not yet been clarified. This study aimed to identify the potential mechanistic pathway through which psychological factors mitigate frailty.MethodsData were collected from June to August 2019 by trained investigators through face-to-face interviews with 375 HIV-positive Chinese adults. Each participant completed structured questionnaires to collect data in respect of their socio-demographic characteristics, and levels of frailty, depression, and resilience. These assessment measures included a self-designed questionnaire, the Tilburg Frailty Indicator (TFI), the 10-item Center for Epidemiological Studies Depression Scale (CES-D-10), and the 10-item Connor-Davidson Resilience Scale (CD-RISC-10). SPSS PROCESS macro was used to analyze the mediation and moderated mediation models.ResultsThe overall prevalence of frailty was 26.4%, and the prevalence of frailty among older and younger adults living with HIV was 22 and 31.4%, respectively. Mediation analysis showed that an association between resilience and frailty was mediated by depression, whereas resilience did not mediate the relationship between depression and frailty. Compared to physical frailty, depression was a stronger mediator of resilience to psychological frailty. We further found that age moderated the indirect effect of resilience on psychological frailty, with resilience being a stronger negative predictor of depression and depression being a stronger positive predictor of psychological frailty for older PLHIV than for younger PLHIV.ConclusionLower levels of resilience and greater levels of depression may be significant risk factors for frailty among PLHIV. Levels of resilience influenced frailty directly and frailty was indirectly affected by depression. Therefore, it is recommended that PLHIV, especially older patients, should be encouraged to establish positive psychological coping strategies to slow the progression of frailty.

Magnesium (Mg) is an essential element for plant growth and development. Rice is an important food crop in the world, but there are few studies on the uptake and translocation of Mg2+ in rice. We used a multi-parent advanced generation inter-cross (MAGIC) population constructed using four parental lines and genotyped by a 55 K rice SNP array for association analysis to locate QTLs related to Mg2+ uptake and translocation in rice at the seedling stage. Four QTLs (qRMg1, qRMg2, qRMg7 and qRMg8) were detected for the root Mg2+ concentration, which explained 11.45-13.08% of the phenotypic variation. The Mg2+ transporter gene, OsMGT1, was within the region of qRMg1. Three QTLs (qSMg3, qSMg7 and qSMg10) were detected for the shoot Mg2+ concentration, which explained 4.30-5.46% of the phenotypic variation. Two QTLs (qTrMg3 and qTrMg8) were found to affect the translocation of Mg2+ from the roots to the shoots, and explained 10.91% and 9.63% of phenotypic variation. qSMg3 and qTrMg3 might be the same, since they are very close to each other on chromosome 3. Analysis of candidate genes in the region of qSMg3 and qTrMg3 through qRT-PCR, complementation assay in the yeast Mg2+ transport-defective mutant CM66, and sequence analysis of the parental lines suggested that LOC_Os03g04360 may play important roles in Mg2+ uptake, translocation and accumulation in rice. Overexpression of LOC_Os03g04360 can significantly increase the Mg2+ concentration in rice seedlings, especially under the condition of low Mg2+ supply.

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) is spreading rapidly around the world and has become a global pandemic. Meteorological factors have been recognized as one of the critical factors that influence the epidemiology and transmission of infectious diseases. In this context, the World Meteorological Organization and scholars at home and abroad have paid extensive attention to the relationships of environment and meteorology with COVID-19. This paper systematically collected and sorted out relevant domestic and foreign studies, and reviewed the latest research progress on the impact of environmental and meteorological factors on COVID-19, classifying them into typical meteorological factors (such as temperature, humidity, and wind speed), local environmental factors (such as indoor enclosed environment, ventilation, disinfection, and air conditioning), and air pollution. Current research evidence suggests that typical meteorological factors, local environmental factors, and air pollutants are closely related to the transmission of COVID-19. However, the results of different studies are still divergent due to uncertainty about the influencing mechanism, and differences in research areas and methods. This review elucidated the importance of environmental and meteorological factors to the spread of COVID-19, and provided useful implications for the control of further large-scale transmission of COVID-19 and the development of prevention and control strategies under different environmental and meteorological conditions.

Abstract Dynamic regulation of QTLs remains mysterious. Single segment substitution lines (SSSLs) and conditional QTL mapping and functional QTL mappings are ideal materials and methods to explore dynamics of QTLs for complex traits. This paper analyzed the dynamics of QTLs on plant height with SSSLs in rice. Five SSSLs were verified with plant height QTLs first. All five QTLs had significant positive effects at one or more developmental stages except QTL1. They interacted each other, with negative effects before 49 d after transplanting and positive effects since then. The five QTLs selectively expressed in specific periods, mainly in the periods from 35 to 42 d and from 49 to 56 d after transplanting. Expressions of epistasis were dispersedly in various periods, negative effects appearing mainly before 35 d. The five QTLs brought the inflexion point ahead of schedule, accelerated growth and degradation, and changed the peak plant height, while their interactions had the opposite effects. The information will be helpful to understand the genetic mechanism for developmental traits.

As a great threat to the normal growth of rice, drought not only restricts the growth of rice, but also affects its yield. Glutathione S-transferases (GSTs) have antioxidant and detoxification functions. In rice, GSTs can not only effectively cope with biological stress, but also play a defense role against abiotic stress. In this study, we selected OsGSTU17, a member gene that was induced by drought, to explore the role of GSTs and analyze their physiological mechanisms that are involved in rice drought tolerance. With the CRISPR/Cas9 knockout system techniques, we obtained two independent mutant lines of osgstu17. After 14 days of drought stress treatment, and then re-supply of the water for 10 days, the survival rate of the osgstu17 mutant lines was significantly reduced compared to the wild-type (WT). Similarly, with the 10% (w/v) PEG6000 hydroponics experiment at the seedling stage, we also found that compared with the WT, the shoot and root biomass of osgstu17 mutant lines decreased significantly. In addition, both the content of the MDA and H2O2, which are toxic to plants, increased in the osgtu17 mutant lines. On the other hand, chlorophyll and proline decreased by about 20%. The activity of catalase and superoxide dismutase, which react with peroxides, also decreased by about 20%. Under drought conditions, compared with the WT, the expressions of the drought stress-related genes OsNAC10, OsDREB2A, OsAP37, OsP5CS1, OsRAB16C, OsPOX1, OsCATA, and OsCATB in the osgtu17 mutant lines were significantly decreased. Finally, we concluded that knocking out OsGSTU17 significantly reduced the drought tolerance of rice; OsGSTU17 could be used as a candidate gene for rice drought-tolerant cultivation. However, the molecular mechanism of OsGSTU17 involved in rice drought resistance needs to be further studied.

AimsThe Ca+/NFAT (Nuclear factor of activated T cells) signaling pathway activation is implicated in the pathogenesis of Kawasaki disease (KD); however, we lack detailed information regarding the regulatory network involved in the human coronary endothelial cell dysfunction and cardiovascular lesion development. Herein, we aimed to use mouse and endothelial cell models of KD vasculitis in vivo and in vitro to characterize the regulatory network of NFAT pathway in KD.Methods and ResultsAmong the NFAT gene family, NFAT2 showed the strongest transcriptional activity in peripheral blood mononuclear cells (PBMCs) from patients with KD. Then, NFAT2 overexpression and knockdown experiments in Human coronary artery endothelial cells (HCAECs) indicated that NFAT2 overexpression disrupted endothelial cell homeostasis by regulation of adherens junctions, whereas its knockdown protected HCAECs from such dysfunction. Combined analysis using RNA-sequencing and transcription factor (TF) binding site analysis in the NFAT2 promoter region predicted regulation by Forkhead box O4 (FOXO4). Western blotting, chromatin immunoprecipitation, and luciferase assays validated that FOXO4 binds to the promoter and transcriptionally represses NFAT2. Moreover, Foxo4 knockout increased the extent of inflamed vascular tissues in a mouse model of KD vasculitis. Functional experiments showed that inhibition NFAT2 relieved Foxo4 knockout exaggerated vasculitis in vivo.ConclusionsOur findings revealed the FOXO4/NFAT2 axis as a vital pathway in the progression of KD that is associated with endothelial cell homeostasis and cardiovascular inflammation development.

NK cells have important functions in resisting cytomegalovirus infection, as they proliferate after viral infection and have certain immunological memory. Here, we report infusion of haploid donor-derived natural killer cells to treat two pediatric patients with Wiskott-Aldrich syndrome (WAS) who were infected with cytomegalovirus after cord blood transplantation (CBT), which successfully cleared the viral infection in both patients.

Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) based on granulocyte colony-stimulating factor plus anti-thymocyte regimens (‘Beijing Protocol’) provides a salvage treatment for patients of acquired severe aplastic anemia (SAA) in China. However, graft- versus -host disease (GVHD) is a major impediment of haplo-HSCT due to human leukocyte antigen disparity. Recently, haplo-HSCT combined with umbilical cord blood (UCB) (haplo-cord HSCT) is performed in clinical trials to potentially reduce the risk of severe GVHD. Nevertheless, studies comparing GVHD in pediatric patients receiving haplo and haplo-cord HSCT for SAA are limited. Objective: The objective of this study was to investigate the impact of UCB co-infusion on GVHD in pediatric patients receiving haplo-HSCT for SAA. Design: We conducted a retrospective study of 91 consecutive SAA children undergoing haploidentical transplantation based on the ‘Beijing Protocol’ with or without co-infusion of UCB in our center. Methods: All patients received uniform non-myeloablative conditioning and GVHD prophylaxis. We compared baseline characteristics and transplant outcomes between the haplo ( n = 35) and haplo-cord ( n = 56) recipients. Results: All 91 patients achieved hematopoietic recovery from haploidentical donors, with a higher incidence of peri-engraftment syndrome observed with the haplo-cord group as compared with the haplo group (75.0% versus 48.6%, p = 0.029). Notably, the haplo-cord group showed a lower incidence of II–IV acute GVHD (aGVHD) than the haplo group (16.1% versus 42.9%, p = 0.002). Observed incidences of chronic GVHD (cGVHD) and moderate to severe cGVHD in the haplo-cord group were also lower than that in the haplo group (25.6% versus 51.3%, p = 0.019; 16.2% versus 41.3%, p = 0.016, respectively). Haplo-cord HSCT was identified as the only factor associated with a lower incidence of II–IV aGVHD and cGVHD in multivariate analysis. However, no differences were observed between the two groups for infections and survival outcomes. Conclusion: Our data indicated that co-infusion of UCB in ‘Beijing Protocol’-based haplo-HSCT may be effective for reducing the risk of severe GVHD in SAA children.

Long non-coding RNAs (lncRNAs) regulate many biological processes in plants, including defense against pathogens and herbivores. Recently, many small ORFs embedded in lncRNAs have been identified to encode biologically functional peptides (small ORF-encoded peptides [SEPs]) in many species. However, it is unknown whether lncRNAs mediate defense against herbivore attack and whether there are novel functional SEPs for these lncRNAs. By sequencing Spodoptera litura-treated leaves at six time-points in Nicotiana tabacum, 22,436 lncRNAs were identified, of which 787 were differentially expressed. Using a comprehensive mass spectrometry (MS) pipeline, 302 novel SEPs derived from 115 tobacco lncRNAs were identified. Moreover, 61 SEPs showed differential expression after S. litura attack. Importantly, several of these peptides were characterized through 3D structure prediction, subcellular localization validation by laser confocal microscopy, and western blotting. Subsequent bioinformatic analysis revealed some specific chemical and physical properties of these novel SEPs, which probably represent the largest number of SEPs identified in plants to date. Our study not only identifies potential lncRNA regulators of plant response to herbivore attack but also serves as a valuable resource for the functional characterization of SEP-encoding lncRNAs.

Durability and capacity of electrode materials, especially the anodes, are the main challenges for aqueous Li-ion batteries. In this work, MoSe2 micron flowers have been synthesized and investigated as anodes for Li+ storage in LiCl aqueous-based electrolytes. In the LiCl solution, the working potential of the MoSe2 anode can reach −1.0 V (vs Ag/AgCl). Yet, its reversible capacity is only ∼14 mAh g−1 (50 C g−1), owing to the absence of Faradaic reactions and the fast deformation of MoSe2. After gelation of the LiCl solution using poly vinyl alcohol (PVA), the activity of water is largely inhibited, and the operating potential is broadened to −1.2 V. In this gel system, the Faradaic reaction of the MoSe2 anode is triggered, and hence its capacity is largely enhanced. With a suitable amount of PVA (LiCl/PVA-20), the MoSe2 electrode can deliver reversible capacities of high as 157 mAh g−1 at 1 A g−1, and 139 mAh g−1 at 2 A g−1, and still high as 100 mAh g−1 after 50 cycles, indicating relative good stability. Using commercial LiMn2O4 as cathode, a full aqueous Li-ion battery was assembled, and a high discharge voltage of ∼1.8 V can be achieved. It is found that not only the activity of water but also the morphology change of the MoSe2 during cycling is inhibited in the gel electrolyte.

This study was designed to elucidate the immunoregulation of Ganoderma lucidum. HPLC fingerprint and spectrum-effect relationship of G. lucidum were established to predict the active compounds and BP neural network model was established to predict the efficacy. Then the target compounds were identified by high resolution mass spectrometry. The results indicated that there are both enhanced immunity and immunosuppressive components in G. lucidum. BP neural network was trained with the common peak area and immune efficacy index of G. lucidum fingerprint as samples, and a combined evaluation system of G. lucidum fingerprint efficacy was established. The correlation coefficient R of BP network model was 0.986 43, and the error of pharmacodynamic prediction results was in the ideal range. Eight compounds were identified by high resolution mass spectrometry. The compounds related to immune activity in G. lucidum were determined in this study.

Class III peroxidases (PODs) are plant-specific enzymes that play significant roles in plant physiological processes and stress responses. However, a comprehensive analysis of the POD gene family in tobacco has not yet been conducted. In this study, 210 non-redundant POD gene members (NtPODs) were identified in tobacco (Nicotiana tabacum) and distributed unevenly throughout 24 tobacco chromosomes. Phylogenetic analysis clustered these genes into six subgroups (I-VI). Gene structure and motif analyses showed the structural and functional diversity among the subgroups. Segmental duplication and purifying selection were the main factors affecting NtPOD gene evolution. Our analyses also suggested that NtPODs might be regulated by miRNAs and cis-acting regulatory elements of transcription factors that are involved in various biological processes. In addition, the expression patterns in different tissues and under various stress treatments were investigated. The results showed that the majority of NtPODs had tissue-specific expression patterns and may be involved in many biotic and abiotic responses. qRT-PCR analyses of different tissues and stress treatments were performed to verify transcriptome patterns. Expression of a green fluorescent protein-NtPOD fusion confirmed the plasma membrane localization of NtPOD121 and NtPOD4. Furthermore, 3D structures provided evidences of membrane-bound peroxidase. These findings provide useful information to better understand the evolution of the NtPOD gene family and lay the foundation for further studies on POD gene function in tobacco.

Background & Aims: Fulminant hepatitis (FH) is a clinical syndrome characterized by sudden and severe liver dysfunction. Dot1L, a histone methyltransferase, is implicated in various physiologic and pathologic processes, including transcription regulation and leukemia. However, the role of Dot1L in regulating inflammatory responses during FH remains elusive. Methods: Propionibacterium acnes (P. acnes)-primed, lipopolysaccharides (LPS)-induced FH was established in C57BL/6 mice and was treated with the Dot1L inhibitor EPZ-5676. Myeloid derived suppressor cells (MDSCs) were depleted by anti-Gr-1 antibody to evaluate their therapeutic roles in Dot1L treatment of FH. Moreover, peripheral blood of patients suffered with FH and healthy controls was collected to determine the expression profile of Dot1L-SOCS1-iNOS axis in their MDSCs. Results: Here we identified that EPZ-5676, pharmacological inhibitor of Dot1L, attenuated the liver injury of mice subjected to FH. Dot1L inhibition led to decreased T helper 1 cell response and expansion of regulatory T cells (Tregs) during FH. Interestingly, Dot1L inhibition didn’t directly target T cells, but dramatically enhanced the immunosuppressive function of MDSCs. Mechanistically, Dot1L inhibition epigenetically suppressed SOCS1 expression, thus inducing inducible nitric oxide synthase (iNOS) expression in a STAT1-dependent manner. Moreover, in human samples, the levels of Dot1L and SOCS1 expression were upregulated in MDSCs, accompanied by decreased expression of iNOS in patients with FH, compared with healthy controls. Conclusions: Altogether, our findings established Dot1L as a critical regulator of MDSC immunosuppressive function for the first time, and highlighted the therapeutic potential of Dot1L inhibitor for FH treatment.

BackgroundIntravenous immunoglobulin (IVIG) showed its therapeutic efficacy on Kawasaki disease (KD). However, the mechanisms by which it reduces systemic inflammation are not completely understood. Dendritic cells (DCs) and T cells play critical roles in the pathogenic processes of immune disorders. Assessing the quantity of DC subsets and T cells and identifying functional molecules present on these cells, which provide information about KD, in the peripheral blood may provide new insights into the mechanisms of immunoglobulin therapy.MethodsIn total, 54 patients with KD and 27 age-matched healthy controls (HCs) were included in this study. The number, percentage, and phenotype of DC subsets and CD4+ T cells in peripheral blood were analyzed through flow cytometry.ResultsPatients with KD exhibited fewer peripheral DC subsets and CD4+ T cells than HCs. Human leucocyte antigen-DR (HLA-DR) expression was reduced on CD1c+ myeloid DCs (CD1c+ mDCs), whereas that on plasmacytoid DCs (pDCs) did not change significantly. Both pDCs and CD1c+ mDCs displayed significantly reduced expression of co-stimulatory molecules, including CD40, CD86. pDCs and CD1c+ mDCs presented an immature or tolerant phenotype in acute stages of KD. Number of circulating pDC and CD1c+ mDC significantly inversely correlated with plasma interleukin-6 (IL-6) levels in KD patients pre-IVIG treatment. No significant differences were found concerning the DC subsets and CD4+ T cells in patients with KD with and without coronary artery lesions. Importantly, these altered quantity and phenotypes on DC subsets and CD4+ T cells were restored to a great extent post-IVIG treatment. T helper (Th) subsets including Th1 and Th2 among CD4+ T cells did not show alteration pre- and post-IVIG treatment, although the Th1-related cytokine IFN-γ level in plasma increased dramatically in patients with KD pre-IVIG treatment.ConclusionspDCs and CD1c+ mDCs presented an immature or tolerant phenotype in acute stages of KD, IVIG treatment restored the quantity and functional molecules of DCs and CD4+ T cells to distinct levels in vivo, indicating the involvement of DCs and CD4+ T cells in the inflammation in KD. The findings provide insights into the immunomodulatory actions of IVIG in KD.

Compounds with regulating glucose metabolism and improving insulin resistance (IR) activity are abundant in nature and can be obtained from several sources. They have high potential to be used to treat diabetes mellitus. These compounds isolated from natural plants can be classified seven categories: terpenoids, alkaloids, quinones, flavonoids, phenols, phenyl propanoids, steroids, and other types of compounds. They exert biological effects by different ways and mechanisms. This review illustrated the potential natural products as a rich resource in regulation of glucose metabolism and IR, as well as their mechanisms.

Rice leaf is a solar panel of photosynthesis and determines the light energy utilization and yield of plants. Leaf numbers appear as S-type or parabola-type growth curves throughout their development. However, the ways in which the genes regulate the process of leaf numbers still remain poorly understood. This paper first identified five QTLs associated with leaf numbers using single-segment substitution lines (SSSLs). Then, the epistatic effects between double QTLs were estimated via the decomposition of the QTL polymerization effects. Additionally, further the expression patterns and functions for these five QTLs and their epistasis were revealed by the methodologies of conditional QTL mapping and functional QTL mapping, respectively. The five SSSLs were detected as having significant additive and/or dominant effects at one or more stages, all of which increased the leaf numbers, except for the negative additive effect of the first SSSL. Seven pairs of QTLs interacted each other via three or four epistatic components, with the opposite effects in the case of single genes, i.e., most epistatic effects were negative. The five QTLs expressed their effects mainly in three stages, namely within 14 days, from 28 days to 42 days, and from 49 days to 63 days after transplantation. Positive effects and negative interactions of the QTLs were observed in the early and the late stages, but opposite interactions were observed in the middle stage. Mainly, three functional parameters, including the inflexion point, the peak value, and the degradation rate, were regulated via the QTL effects and their opposite interactions. This paper uncovered the genetic rule of five QTLs on the leaf numbers, including the interaction, expression, and function features. The information will be helpful to understand the genetic mechanism for developmental traits.

BackgroundSepsis is a complex systemic immune dysfunction syndrome induced by infection. Sepsis has a high mortality rate, with most patients dying due to systemic organ failure or secondary infection. Dendritic cells (DCs) are professional antigen-presenting cells. Upon infection with microbes, DCs are activated to induce adaptive immune responses for controlling infection. DC generation and function are impaired during sepsis; however, the underlying mechanisms remain largely unknown.MethodsPeripheral blood samples from sepsis patients were collected to examine DC subsets, DC progenitors, and apoptosis of DCs by flow cytometer. In vitro induction of DCs from hematopoietic stem/progenitor cells were established and a variety of sepsis-associated inflammatory mediators [e.g., interferon-gamma (IFN-γ), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and granulocyte-colony stimulating factor (G-CSF)] and Lipopolysaccharide (LPS) were determined for the impact on DC generation and function in vitro.ResultsOur results demonstrate that sepsis-induced systemic inflammation impairs the capacity of hematopoietic stem and progenitor cells (HSPCs) to produce DCs, including conventional DCs (cDCs) and plasmacytoid DCs (pDCs). We investigated peripheral blood (PB) samples from 34 pediatric patients on days 1 to 7 following diagnosis. Compared to healthy donors (n = 18), the sepsis patients exhibited a significantly fewer percentage and number of pDCs and cDCs, and a lower expression of antigen presenting molecule HLD-DR and co-stimulatory molecules (e.g., CD86) on the surface of DCs. This sepsis-induced DC impairment was associated with significantly increased apoptotic death of DCs and marked decreases of progenitor cells that give rise to DCs. Furthermore, we observed that among the tested sepsis-associated cytokines (e.g., IFN-γ, IL-1β, TNF-α, and G-CSF), G-CSF and IFN-γ impaired DC development from cultured HSPCs. G-CSF also markedly decreased the expression of HLA-DR on HSPC-derived DCs and their cytokine production, including IL-12 and IFN-β.ConclusionsCollectively, these findings indicate that sepsis impairs the survival of functional DCs and their development from HSPCs. Strategies for improving DC reconstitution following sepsis may restore DC progenitors and their associated function.

Zinc (Zn) deficiency and cadmium (Cd) stress are severe threats to the growth and development of plants. Increasing Zn content and/or decreasing Cd content in grain are also important objectives of rice breeding. However, the molecular mechanisms of Zn deficiency tolerance (ZDT) and Cd stress tolerance (CDT) are largely unknown in rice. Here, we report that a NAM/CUC2-like transcription factor, OsNAC15, contributes to ZDT and CDT in rice. Knockout of OsNAC15 reduced ZDT and CDT at the vegetative stage. OsNAC15 expresses in all tissues of different developmental stages, and is repressed by Zn deficiency and induced by Cd stress. OsNAC15 is a functional transcription factor with transactivation and DNA binding activities. Expression analysis of rice ZIP family genes suggested that the knockout of OsNAC15 activates or inhibits their transcriptions under Zn deficiency or Cd stress conditions. The yeast one-hybrid assay, transient transcriptional activity assay using the dual-luciferase reporter system and electrophoretic mobility shift assay demonstrated that OsNAC15 directly binds to the zinc deficiency-responsive element motifs in the promoters of OsZIP7 and OsZIP10 to repress their transcriptions. The OsNAC15–OsZIP7/10 module is an essential foundation for further study on the regulatory mechanisms of ZDT and CDT in rice.

This paper studied the dynamic process of a dual-trolley overhead crane transshipping rigid-body cargo with degrees of spatial freedom. By taking the tensile stiffness of wire rope, the bending stiffness of box girder and the mass of cargo as variables, six different working conditions were calculated. The influences of the variables on spatial movement of slender cargo were analyzed. To verify the presented analytic model, a virtual prototype model was constructed by using the commercial software ADAMS and ANSYS. The consistency of the calculation results from the two different models proves the effectiveness of the analytic model presented in this paper.

Abstract Background Fully understanding the developmental process of hepatic stem cells (HSCs) and the mechanisms of their committed differentiation is essential for optimizing the generation of functional hepatocytes for cell therapy in liver disease. Delta-like 1 homolog (Dlk1), primarily the membrane-bound form (Dlk1M), is generally used as a surface marker for fetal hepatic stem cell isolation, while its soluble form (Dlk1S) and the functional roles of different Dlk1 isoforms in HSC differentiation remain to be investigated. Methods Hepatic spheroid-derived cells (HSDCs) were isolated from E12.5 mouse livers to obtain Dlk1+ and Dlk1−subpopulations. Colony formation, BrdU staining, and CCK8 assays were used to evaluate the cell proliferation capacity, and hepatic/cholangiocytic differentiation and osteogenesis/adipogenesis were used to assess the multipotency of the two subpopulations. Transformation of Dlk1+ cells into Dlk1− cells was detected by FACS, and the expression of Dlk1 isoforms were measured by western blot. The distinct roles and regulatory mechanisms of Dlk1 isoforms in HSC differentiation were investigated by overexpressing Dlk1M. Results HSDCs were capable of differentiating into liver and mesenchymal lineages, comprising Dlk1+ and Dlk1− subpopulations. Dlk1+ cells expressed both Dlk1M and Dlk1S and lost expression of Dlk1M during passaging, thus transforming into Dlk1− cells, which still contained Dlk1S. Dlk1− cells maintained a self-renewal ability similar to that of Dlk1+ cells, but their capacity to differentiate into cholangiocytes was obviously enhanced. Forced expression of Dlk1M in Dlk1− cells restored their ability to differentiate into hepatocytes, with an attenuated ability to differentiate into cholangiocytes, suggesting a functional role of Dlk1 in regulating HSC differentiation in addition to acting as a biomarker. Further experiments illustrated that the regulation of committed HSC differentiation by Dlk1 was mediated by the AKT and MAPK signaling pathways. In addition, bFGF was found to serve as an important inducement for the loss of Dlk1M from Dlk1+ cells, and autophagy might be involved. Conclusions Overall, our study uncovered the differential expression and regulatory roles of Dlk1 isoforms in the commitment of HSC differentiation and suggested that Dlk1 functions as a key regulator that instructs cell differentiation rather than only as a marker of HSCs. Thus, our findings expand the current understanding of the differential regulation of bi-potential HSC differentiation and provide a fine-tuning target for cell therapy in liver disease.

Patrinia scabiosaefolia is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the discovery of nine unique iridoids and iridoid glycosides, including three new iridoids (1-3) and six previously unknown irioid glycosides (5-10), and one known compound (4). Among them, compound 1 was a deformed iridoid, while compounds 3, 5-7, and 10 formed a new ring in their skeletons which was uncommon in this genus. For compound 3, the new ring existed between C-3 and C-10, while a 1,3-dioxane appeared between C-7 and C-10 in compounds 5-7 and 10. Moreover, compound 10 was a bis-iridoid glycoside, which was the first reported in P. scabiosaefolia. And the sugar of irioid glycosides (5-10) was glucose at C-11, except in 9 which had a 5-deoxyglucose moiety. All their structures were confirmed based on the extensive spectroscopic analysis, including IR, UV, HR-ESI-MS, ECD, and 1D- and 2D-NMR experiments. Their cytotoxic activities against HL-60, A-549, SMMC-7721, MCF-7, SW480 were also tested.

Poria is a common Traditional Chinese Medicine in clinic. In recent years, the chemical and pharmacological studies of Poria have made great progress, triterpenes and polysaccharides have been isolated, and various types of compounds containing lipids, octanoic acids, fatty acids, and trace elements have been found. In this paper, we reviewed the literature, summarized the main compound types, and reviewed in detail their pharmacological effects in antitumor, immunomodulatory, effects on kidney, hepatoprotective activity, effects on blood sugar, antioxidant effects, anti-inflammatory effects, effects on the gut, antidepressant, and so on, and also categorized the compounds with the same or similar pharmacological effects to provide a reference for the in-depth study of the material basis of the pharmacological effect, quality standards, and pharmacological activity of Poria.

Liquid storage tanks are lifeline structures and strategically very important. Heavy damages or even collapse of these facilities subjected to strong earthquakes may cause disastrous consequences. In this paper, the seismic response of a multistage series liquid storage tank was simulated by a finite element method and verified by a scaled-down experiment. The structural flexibility of the tank and the liquid-structure coupling characteristics between the liquid and tank wall were considered in the research. A multimass-block and spring model was employed to be equivalent to the longitudinal vibration of the liquid in the storage tank. The relationships between the connection springs and the elements of the stiffness matrix were explicitly deduced. The seismic response analysis of a four-stage series liquid tank was carried out, and the acceleration response, the stress response of the tank, and the vertical vibration of the liquid were obtained. The experimental results are in good agreement with the simulation results, which verifies the effectiveness of the modeling method in this paper.

The plants from genus Origanum are common folk Chinese herbs used to treat a variety of diseases. They are also used as a spice, a seasoning, and an ornament. Origanum plants are rich in essential oils and also have other compounds including terpenoids, flavonoids, organic acids, and sterols. They have a variety of biological activities such as antispasmodic, anti-inflammatory, growth-promoting, antibacterial, antioxidant, and anticancer properties. The chemical components and biological effects of genus Origanum were summarized by different scientific databases such as Web of Science, SciFinder, Baidu Scholar, PubMed, ScienceDirect, and SpringerLink. In conclusion, recent studies were mainly focused on the activities of their essential oils. The research studies for nonvolatile constituents and their pharmacological activities are few. Therefore, research on compounds in genus Origanum plants can be strengthened and their application prospect can be explored so as to make better use of the resources of these plants.

Drought and salinity stresses are significant abiotic factors that limit rice yield. Exploring the co-response mechanism to drought and salt stress will be conducive to future rice breeding. A total of 1748 drought and salt co-responsive genes were screened, most of which are enriched in plant hormone signal transduction, protein processing in the endoplasmic reticulum, and the MAPK signaling pathways. We performed gene-coding sequence haplotype (gcHap) network analysis on nine important genes out of the total amount, which showed significant differences between the Xian/indica and Geng/japonica population. These genes were combined with related pathways, resulting in an interesting mechanistic draft called the ‘gcHap-network pathway’. Meanwhile, we collected a lot of drought and salt breeding varieties, especially the introgression lines (ILs) with HHZ as the parent, which contained the above-mentioned nine genes. This might imply that these ILs have the potential to improve the tolerance to drought and salt. In this paper, we focus on the relationship of drought and salt co-response gene gcHaps and their related pathways using a novel angle. The haplotype network will be helpful to explore the desired haplotypes that can be implemented in haplotype-based breeding programs.

This paper presents methods for the 2019 PHM Conference Data Challenge developed by the team named "Angler". This Challenge aims to estimate the fatigue crack length of a type of aluminum structure using ultrasonic signals at the current load cycle and to predict the crack length at multiple future load cycles (multiple-step-ahead prediction) as accurately as possible. For estimating crack length, four crack-sensitive features are extracted from ultrasonic signals, namely, the first peak value, root mean square value, logarithm of kurtosis, and correlation coefficient. An ensemble linear regression model is presented to map these features and their second-order interactions with the crack length. The Best Subset Selection method is employed to select the optimal features. For predicting crack length, variations of the Paris’ law are derived to describe the relationships between the crack length and the number of load cycles. The material parameters and stress range of Paris’ law are learned using the Genetic Algorithm. These parameters will be updated based on the previous-step predicted crack length. After that, the crack length corresponding to a future load cycle number for either the constant amplitude load case or variable amplitude load case is predicted. The presented methods achieved a score of 16.14 based on the score-calculation rule provided by the Data Challenge committees, and was ranked third best among all participating teams.

Plants of Delphinium are herbal medicine used in the Tibet region with whole grass as a drug, which have the effects of analgesic, antibacterial, antipyretic, and anticancer. The main bioactive compounds are alkaloids, flavonoids, and sterols. This review summarized the compounds and pharmacological effects of Delphinium and provides a reference for further research on Delphinium.

Single-molecule techniques such as electron tunneling and atomic force microscopy have attracted growing interests in protein sequencing. For these methods, it is critical to refine and stabilize the protein sample to a “suitable mode” before applying a high-fidelity measurement. Here, we show that a planar heterostructure comprising boronic graphene (BC3) and nitrogenized graphene (C3N) sandwiched stripe (BC3/C3N/BC3) is capable of the effective stretching and confinement of three types of intrinsically disordered proteins (IDPs), including amyloid-β (1–42), polyglutamine (Q42), and α-Synuclein (61–95). Our molecular dynamics simulations demonstrate that the protein molecules interact more strongly with the C3N stripe than the BC3 one, which leads to their capture, elongation, and confinement along the center C3N stripe of the heterostructure. The conformational fluctuations of IDPs are substantially reduced after being stretched. This design may serve as a platform for single-molecule protein analysis with reduced thermal noise.

During an immune response naive CD8+ T cells can differentiate into either effector or memory T cells. Here the authors show that Akt-mediated phosphorylation of the epigenetic regulator Ezh2 is critical for the generation of an anti-tumor CD8 T cell response and promotes the expansion of memory-precursors.

Soil salinization caused by the accumulation of sodium can decrease rice yield and quality. Identification of rice salt tolerance genes and their molecular mechanisms could help breeders genetically improve salt tolerance. We studied QTL mapping of populations for rice salt tolerance, period and method of salt tolerance identification, salt tolerance evaluation parameters, identification of salt tolerance QTLs, and fine-mapping and map cloning of salt tolerance QTLs. We discuss our findings as they relate to other genetic studies of salt tolerance association.

Cadmium (Cd), a heavy metal toxic to humans, easily accumulates in rice grains. Rice with unacceptable Cd content has become a serious food safety problem in many rice production regions due to contaminations by industrialization and inappropriate waste management. The development of rice varieties with low grain Cd content is seen as an economic and long-term solution of this problem. The cation/H+ exchanger (CAX) family has been shown to play important roles in Cd uptake, transport and accumulation in plants. Here, we report the characterization of the rice CAX family. The six rice CAX genes all have homologous genes in Arabidopsis thaliana. Phylogenetic analysis identified two subfamilies with three rice and three Arabidopsis thaliana genes in both of them. All rice CAX genes have trans-member structures. OsCAX1a and OsCAX1c were localized in the vacuolar while OsCAX4 were localized in the plasma membrane in rice cell. The consequences of qRT-PCR analysis showed that all the six genes strongly expressed in the leaves under the different Cd treatments. Their expression in roots increased in a Cd dose-dependent manner. GUS staining assay showed that all the six rice CAX genes strongly expressed in roots, whereas OsCAX1c and OsCAX4 also strongly expressed in rice leaves. The yeast (Saccharomyces cerevisiae) cells expressing OsCAX1a, OsCAX1c and OsCAX4 grew better than those expressing the vector control on SD-Gal medium containing CdCl2. OsCAX1a and OsCAX1c enhanced while OsCAX4 reduced Cd accumulation in yeast. No auto-inhibition was found for all the rice CAX genes. Therefore, OsCAX1a, OsCAX1c and OsCAX4 are likely to involve in Cd uptake and translocation in rice, which need to be further validated.