Search

Background Congenital anatomic abnormalities of fallopian tubes and ovaries are rarely reported. Herein, we describe four cases of abnormal ovarian descent during laparoscopic surgery with abnormal anatomy of fallopian tube, without abnormal uterine development and urinary system abnormalities. These cases are analyzed by their clinical features and their effects on reproductive function. Case presentation For patients with undescended ovary, the upper part of the unilateral/bilateral ovary decline was much higher than that of the common iliac vessel bifurcation, and the fallopian tube on the same side opened in the para-colonic sulcus. Among four patients, two cases had primary infertility, one case had tubal pregnancy rupture and bleeding, and one case had uterine leiomyoma. The development of uterus was normal in all the four patients, and there was no abnormal development of urinary system. During the infertility examination, hysterosalpingography (HSG) suggestion of oviduct lift was a sign for possible undescended ovarian. The pelvic B-ultrasound examination was limited to discover ovarian maldescent. Conclusion Laparoscopy was the gold standard for the diagnosis of poor ovarian decline. When B-ultrasound prompts one-sided or double-sided "ovary display is unclear" or detects "shrinking small ovaries", it might be ovarian maldescent. When there is periodic post-sacral spinal pain, MRI positioning or HSG can be used for diagnosis.

Summary Unlike in metazoans, the stepwise biogenesis of microRNAs (miRNAs) occurs within the nucleus in plants. Whether or how the major steps in miRNA biogenesis are coordinated is largely unknown. Here, we show that the plant TREX-2 complex promotes multiple steps in miRNA biogenesis, including transcription, processing and nuclear export. Core subunits of TREX-2, THP1 and SAC3A, interact and co-localize with RNA Polymerase II to promote the transcription of MIR genes in the nucleoplasm. TREX-2 interacts with the microprocessor component SERRATE and promotes the formation of Dicing bodies in the nucleoplasm. THP1 also interacts and co-localizes with the nucleoporin protein NUP1 at the nuclear envelope. NUP1 and THP1 promote the nuclear export of miRNAs and AGO1. These results suggest that TREX-2 coordinates the transcription, processing and export steps in miRNA biogenesis to ensure efficient miRNA production.

Consumption of functional juice is becoming increasingly popular. This study aimed to evaluate the effect of probiotic fermentation with Bacillus sp. DU-106; Lactobacillus planturum Lp-43 and Lactobacillus rhamnosus Lr-156 on the biochemical and functional characteristics, antioxidant activities and storage stability of Dendrobium officinale and banana (DOB) juice. The cell levels of the lactic acid bacteria reached near 9 log copies/mL after fermentation at 32 °C for 36 h and could keep in this level after storage at 4 °C for 28 days. After fermentation, total acidity, flavonoids and polysaccharide contents of DOB juice increased, while pH, dissolved oxygen, nitrite, nitrate, vitamin C, β-carotene, sugar contents and antioxidant capacity slightly decreased. Compared with nonfermented DOB juice, polyphenol oxidase (PPO) and peroxidase (POD) activities of fermented DOB decreased significantly, but the color value and the content of total phenols and vitamin C decreased slightly in fermented DOB juice during storage. Overall, the probiotic fermentation with selected strains could improve the quality the DOB juice, enhance antioxidant capacity and storage stability, and destroy accumulation of nitrite and nitrate during storage. Findings of this study would help in the development of beneficial beverages in industrial production.

Objectives: Ingestion of a foreign body can cause different degrees of damage to esophagus, and several complications are potentially life-threatening if not properly handled. The aortic injury caused by a perforating esophageal foreign body is rare but lethal. The optimal management still remains controversial. The purpose of this report is to describe our experience in the management of the aortic injury caused by esophageal foreign body ingestion. Methods: Between January 2015 and December 2015, we retrospectively enrolled cases of esophageal perforation involving the aorta by foreign body. The general parameters, esophageal foreign body, types of aortic injury, treatment, and outcome were analyzed. Additionally, we reviewed the literature of the management of esophageal perforation involving the aorta caused by foreign bodies. The study was approved by the ethics committee of the First Affiliated Hospital, College of Medicine, Zhejiang University, and the need for informed consent was waived (Quick review 2019, No. 609). Results: Three cases of esophageal perforation involving the aorta by foreign body was selected in the study. Two male and 1 female patients (range, 51–58 years old) with the aorta involvement caused by a perforating foreign body in the esophagus in 3 forms were identified, including 1 patient with mycotic aortic pseudoaneurysm, 1 patient with aortoesophageal fistula and 1 patient with the aortic intramural hematoma. One patient died of the rupture of the pseudoaneurysm during the preparation of the surgery. The other 2 patients were cured with a multidisciplinary approach, which is an urgent thoracic endovascular aortic repair followed by mediastinal debridement/drainage or endoscopic retrieval. Two of 3 patients were survived until now. Conclusion: The management of the aortic injury caused by esophageal foreign body injury is challenging. Early diagnosis and multidisciplinary management is crucial.

Intractable or recurrent chronic itch greatly reduces the patients' QOL and impairs their daily activities. In this study, we investigated whether there are certain key signaling molecules downstream of the recently identified peptides mediating itch in the spinal cord. RNA sequencing analysis of mouse spinal cord in chronic itch models induced by squaric acid dibutylester and imiquimod showed that extracellular signal-regulated kinase (ERK) 1/2 cascade is the most significantly upregulated gene cluster in both models. In four different mouse models of chronic itch, sustained ERK phosphorylation was detected mainly in spinal neurons, and MAPK/ERK kinase inhibitors significantly inhibited chronic itch in these models. Phosphorylated ERK was observed in the interneurons expressing the receptors of different neuropeptides for itch, including gastrin-releasing peptide receptor, natriuretic peptide receptor A, neuromedin B receptor, and sst2A. Blocking gastrin-releasing peptide receptor and natriuretic peptide receptor A by genetic approaches or toxins in mice significantly attenuated or ablated spinal phosphorylated ERK. When human embryonic kidney 293T cells transfected with these receptors were exposed to their respective agonists, ERK was the most significantly activated intracellular signaling molecule. Together, our work showed that phosphorylated ERK is a unique marker for itch signal transmission in the spinal cord and an attractive target for the treatment of chronic itch.

A water-soluble polysaccharide named CYP-1 was isolated from Chinese yam. CYP-1 was characterized as a mannoglucan having a backbone consisting predominately of 1,4-α-linked Glcp branched at O-2, O-3, and O-6 position by t-α-linked Manp with a molecular weight of 2.86 kDa. CYP-1 could inhibit the overproduction of pro-inflammatory cytokines (such as TNF-α and IL-1β) in LPS-induced RAW 264.7 cells and DSS-induced colitis mice. Oral administration of CYP-1 dramatically alleviated colonic pathological damage, suppressed the activation of colonic inflammatory signaling pathways (such as NF-κB and NLRP3 inflammasome), recovered the mRNA expression of junctional proteins (such as ZO-1, claudin-1, occludin, and connexin-43), and modulated the gut microbiota by decreasing the abundances of Alistipes, Helicobacter, and an unidentified Enterobacteriaceae, in DSS-induced colitis mice. Overall, the present study elucidated that a new polysaccharide structure CYP-1 from Chinese yam and its therapeutic potential as a prebiotic for the prevention of inflammatory bowel disease.

Exquisitely regulated plastid-to-nucleus communication by retrograde signaling pathways is essential for fine-tuning of responses to the prevailing environmental conditions. The plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) has emerged as a stress signal transduced into a diverse ensemble of response outputs. Here we demonstrate enhanced phytochrome B protein abundance in red-light grown MEcPP-accumulating mutant (ceh1) plant relative to wild-type seedlings. We further establish MEcPP-mediated coordination of phytochrome B with auxin and ethylene signaling pathways, and uncover differential hypocotyl growth of red-light grown seedlings in response to these phytohormones. Genetic and pharmacological interference with ethylene and auxin pathways outline the hierarchy of responses, placing auxin epistatic to the ethylene signaling pathway. Collectively, our finding establishes the key role of a plastidial retrograde metabolite in orchestrating the transduction of a repertoire of signaling cascades, and positions plastids at the zenith of relaying information coordinating external signals and internal regulatory circuitry to secure organismal integrity.Two sentence summaryThe plastidial retrograde metabolite, MEcPP, orchestrates coordination of light and hormonal signaling cascade through induction of phytochrome B abundance and modulation of auxin and ethylene levels for optimal adaptive responses to light environment.

supplemental_material_(2) for Comprehensive Analysis of a Long Noncoding RNA-Associated Competing Endogenous RNA Network in Wilms Tumor by Feng Zhang, Liping Zeng, Qinming Cai, Zihao Xu, Ruida Liu, Haicheng Zhong, Robert Mukiibi, Libin Deng, Xiaoli Tang and Hongbo Xin in Cancer Control

The Active Disturbance Rejection Control (ADRC) algorithm is becoming more and more popular in the field of controller design. Compared with the traditional PID control algorithm, ADRC algorithm can achieve better performance. ADRC consists of a tracking differentiator, a feedback control law, and an extended state observer. For the self-balancing two-wheeled car control, it can be taken as a single-stage inverted pendulum model. Based on the formulated mathematical differential equation model, we apply the ADRC algorithm to control the self-balancing car. Furthermore, to show the effectiveness of ADRC, we compare its performance with PID controller by Simulink simulation tool of MATLAB. Simulation results show that the ADRC algorithm performs better than PID in smaller overshoot, lower steady-state error and faster convergence rate.

Human urine is traditionally considered to be sterile, and whether the urine harbours distinct microbial communities has been a matter of debate. Potential links between female urine and reproductive tract microbial communities is currently not clear. Here, we collected urine samples from 147 Chinese women of reproductive age and explored the nature of colonization by 16S rRNA gene amplicon sequencing, quantitative real-time PCR, and live bacteria culture. To demonstrate the utility of this approach, the intra-individual Spearman’s correlation was used to explore the relationship between urine and multiple sites of the female reproductive tract. PERMANOVA was also performed to explore potential correlations between the lifestyle and various clinical factors and urinary bacterial communities. Our data demonstrated distinct bacterial communities in urine, indicative of a non-sterile environment. Streptococcus-dominated, Lactobacillus-dominated, and diverse type were the three most common urinary bacterial community types in the cohort. Detailed comparison of the urinary microbiota with multiple sites of the female reproductive tract microbiota demonstrated that the urinary microbiota were more similar to the microbiota in the cervix and uterine cavity than to those of the vagina in the same women. Our data demonstrate the potential connectivity among microbiota in the female urogenital system and provide insight and resources for exploring diseases of the urethra and genital tract.

BACKGROUND Gastric carcinoma high expressed transcript 1 (GHET1) is a long noncoding RNA (lncRNA) that is aberrantly upregulated in numerous cancers. Here we carried out a systematical meta-analysis to investigate the potential prognostic and clinicopathologic significance of lncRNA GHET1 expression in multiple types of malignant tumors. METHODS A systematic document retrieval of the online databases Embase, PubMed, and CNKI for studies relevant to the connection between lncRNA GHET1 level and clinical result of tumors was conducted (up to May 8, 2019). The aggregated odds rates (ORs)/hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the relationship. RESULTS Nine hundred twenty carcinoma patients were enrolled from 12 studies in the present study. The results revealed that increased GHET1 expression was obviously related to worse overall survival (OS) (pooled HR = 2.75, 95% CI: 2.18 - 3.45, p < 0.001). Subgroup analysis results indicated that high GHET1 levels present a stronger connection with poor OS in digestive system cancers. In addition, cancer patients with high GHET1 levels are likely to have distant metastasis (DM) (OR = 12.5, 95% CI: 2.31 - 66.67, p = 0.003), lymph node metastasis (LNM) (OR = 4.29, 95% CI: 2.930 - 6.29, p < 0.001), and advanced clinical staging OR = 4.6, 95% CI: 3.33 - 6.34, p < 0.001), but GHET1 expression was not correlated with gender (p = 0.586), age (p = 0.332), tumor differentiation (p = 0.550), or tumor size (p = 0.084). CONCLUSIONS Overexpression of GHET1 may be a convincing adverse prognostic factor that contributes to the clinical decision-making procedure of cancer treatment.

Gene duplications provide evolutionary potentials for generating novel functions, while polyploidization or whole genome duplication (WGD) doubles the chromosomes initially and results in hundreds to thousands of retained duplicates. WGDs are strongly supported by evidence commonly found in many species-rich lineages of eukaryotes, and thus are considered as a major driving force in species diversification. We performed comparative genomic and phylogenomic analyses of 59 public genomes/transcriptomes and 46 newly sequenced transcriptomes covering major lineages of angiosperms to detect large-scale gene duplication events by surveying tens of thousands of gene family trees. These analyses confirmed most of the previously reported WGDs and provided strong evidence for novel ones in many lineages. The detected WGDs supported a model of exponential gene loss during evolution with an estimated half-life of approximately 21.6 million years, and were correlated with both the emergence of lineages with high degrees of diversification and periods of global climate changes. The new datasets and analyses detected many novel WGDs widely spread during angiosperm evolution, uncovered preferential retention of gene functions in essential cellular metabolisms, and provided clues for the roles of WGD in promoting angiosperm radiation and enhancing their adaptation to environmental changes.

As an important weak target detection method, Duffing oscillator is very effective in detecting signals with very low signal-to-noise ratio. However, the accurate discrimination between chaotic and periodic states is a crucial problem and that is the prerequisite for using the Duffing oscillator. Conventionally, the Lyapunov exponent is used as an index to identify different states, but as this indicator has the problem of heavy computation cost, slow convergence rate, and requires a mass of data, its application becomes seriously limits. To solve this problem, a novel method for state identification of the Duffing oscillator based on extreme learning machine (ELM) is proposed. The feature data, as the input of ELM, are extracted from the phase diagram and the time series of the Duffing oscillator. Three effective features are extracted in this letter, i.e., ratio of points in and out of the closed region, average distance, and power spectrum. Computer simulations are presented to validate the proposed method and demonstrate that the state classification performance is superior to other related methods with higher computation efficiency, faster convergence rate, and better accuracy.

Multiple sets of spring, spring seat structures are uniformly arranged in circumferential short spring dual mass flywheel (DMF), which generally have a symmetrical structure. The internal springs and spring seats are constrained by the shape of the primary flywheel and the secondary flywheel. At different rotational speeds, the springs and spring seats have different centrifugal forces. To study the dynamic characteristics of the DMF including torque and stiffness with considering the influence of centrifugal force and friction, the discrete method is used to analyze the mechanical actions of the transmission parts in DMF. The torque action between the spring seat and the secondary flywheel is deduced. The dynamic characteristics of the DMF are obtained through analyzing and calculating. Due to the symmetry of the structure, the torque transmitted and the stiffness of the DMF also have specific symmetrical characteristics. Namely, at two relative rotational angles of the same magnitude and opposite direction, the magnitude of the transmitted torque is the same, the direction is opposite. The magnitude and direction of stiffness are the same. The influence of speed, friction coefficient, spring mass, and spring seat mass on the torque and stiffness characteristics are analyzed. Finally, the theoretical analysis is proved to be valid by the torque characteristics test of DMF.

In Arabidopsis thaliana, the MOS4-ASSOCIATED COMPLEX (MAC) is required for defense and development. The evolutionarily conserved, putative RNA helicase MAC7 is a component of the Arabidopsis MAC, and the human MAC7 homolog, Aquarius, is implicated in pre-mRNA splicing. Here, we show that mac7-1, a partial loss-of-function mutant in MAC7, and two other MAC subunit mutants, mac3a mac3b and prl1 prl2 (pleiotropic regulatory locus), exhibit reduced microRNA (miRNA) levels, indicating that MAC promotes miRNA biogenesis. The mac7-1 mutant shows reduced primary miRNA (pri-miRNA) levels without affecting miRNA gene (MIR) promoter activity or the half-life of pri-miRNA transcripts. As a nuclear protein, MAC7 is not concentrated in dicing bodies, but it affects the localization of HYPONASTIC LEAVES1 (HYL1), a key protein in pri-miRNA processing, to dicing bodies. Immunoprecipitation of HYL1 retrieved 11 known MAC subunits, including MAC7, indicating association between HYL1 and MAC. We propose that MAC7 links MIR transcription to pri-miRNA processing. RNA-seq analysis showed that downregulated genes in MAC subunit mutants are mostly involved in plant defense and stimulus responses, confirming a role of MAC in biotic and abiotic stress responses. We also discovered global intron retention defects in mutants in three subunits of MAC, thus linking MAC function to splicing in Arabidopsis.

Staphylococcal enterotoxin A (SEA) is well known as a superantigen and is highly potent in activating T lymphocytes. And it has been used clinically as an immunomodifier in the treatment of a number of tumors for years. However, the mechanism of its action remains largely unclear. In this study, SEA was found to significantly inhibit the proliferation and induce the death of human lung carcinoma A549 cells when co-cultured with human peripheral blood mononuclear cells (PBMCs). SEA could also induce the proliferation of human PBMCs and stimulate human PBMCs to release a wide range of cytokines that have broad anti-tumor activities such as IFN-γ, TNF-α, IL-2. Furthermore, SEA was found in PBMCs to induce a rapid and long-lasting phosphorylation of extracellular signal-regulated kinases (ERKs) which was significantly inhibited by MEK/ERK pathway inhibitors U0126 and PD0325901, and a late onset of phosphorylation of signal transducers and activators of transcription (STATs) which was significantly inhibited by a pan-JAK inhibitor Pyridone 6 (P6). Unexpectedly constitutive ERK or STATs phosphorylation was also significantly inhibited by P6 or U0126 in a dose-dependent manner, respectively. Summing up, our data reveal SEA may function as a novel protein drug used for cancer immunotherapy via inducing activation of PBMCs, immune cell crosstalk-dependent activation of ERK and STATs, and production of tumor-suppressive cytokines.

Explosive diversification is widespread in eukaryotes, making it difficult to resolve phylogenetic relationships. Eudicots contain c. 75% of extant flowering plants, are important for human livelihood and terrestrial ecosystems, and have probably experienced explosive diversifications. The eudicot phylogenetic relationships, especially among those of the Pentapetalae, remain unresolved. Here, we present a highly supported eudicot phylogeny and diversification rate shifts using 31 newly generated transcriptomes and 88 other datasets covering 70% of eudicot orders. A highly supported eudicot phylogeny divided Pentapetalae into two groups: one with rosids, Saxifragales, Vitales and Santalales; the other containing asterids, Caryophyllales and Dilleniaceae, with uncertainty for Berberidopsidales. Molecular clock analysis estimated that crown eudicots originated c. 146 Ma, considerably earlier than earliest tricolpate pollen fossils and most other molecular clock estimates, and Pentapetalae sequentially diverged into eight major lineages within c. 15 Myr. Two identified increases of diversification rate are located in the stems leading to Pentapetalae and asterids, and lagged behind the gamma hexaploidization. The nuclear genes from newly generated transcriptomes revealed a well-resolved eudicot phylogeny, sequential separation of major core eudicot lineages and temporal mode of diversifications, providing new insights into the evolutionary trend of morphologies and contributions to the diversification of eudicots.

Background: Genomic DNA methylation plays an important role in both the occurrence and development of bladder cancer. Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer. Similar to other flavonoids, Kae possesses a flavan nucleus in its structure. This structure was reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs). However, whether Kae can inhibit DNA methylation remains unclear. Methods: Nude mice bearing bladder cancer were treated with Kae for 31 days. The genomic DNA was extracted from xenografts and the methylation changes was determined using an Illumina Infinium HumanMethylation 450 BeadChip Array. The ubiquitination was detected using immuno-precipitation assay. Results: Our data indicated that Kae modulated DNA methylation in bladder cancer, inducing 103 differential DNA methylation positions (dDMPs) associated with genes (50 hyper-methylated and 53 hypo-methylated). DNA methylation is mostly relied on the levels of DNMTs. We observed that Kae specifically inhibited the protein levels of DNMT3B without altering the expression of DNMT1 or DNMT3A. However, Kae did not downregulate the transcription of DNMT3B. Interestingly, we observed that Kae induced a premature degradation of DNMT3B by inhibiting protein synthesis with cycloheximide (CHX). By blocking proteasome with MG132, we observed that Kae induced an increased ubiquitination of DNMT3B. These results suggested that Kae could induce the degradation of DNMT3B through ubiquitin-proteasome pathway. Conclusion: Our data indicated that Kae is a novel DNMT3B inhibitor, which may promote the degradation of DNMT3B in bladder cancer.

A cooling plant by using lake water source was proposed to cool the space in data centers. It combines free cooling technology and variable capacity technology to remove heat and reduce energy consumption effectively. In this paper, firstly, the control strategies for this cooling plant were proposed. Then, a detailed annual energy consumption model with considering the effect of the dynamic heat dissipation characteristics of servers, lake water temperature, outdoor weather conditions, and cooling plant thermal performance, will be established to evaluate the performance and energy efficiency of this cooling plant under different load factors. The results show the mode 1 and mode 2 of this cooling plant are 67.6% and 32.4% of the year’s running time, respectively. The average EER of the cooling plant under different load factor ranges from 16.8~49.3, and the average PUE value ranges from 1.11 to 1.15 under different load factors, which demonstrates this cooling plant poses higher energy efficiency than the conventional cooling plant for the data centers.

The influences of urbanization on weather in Guangdong Province, China, were studied using the Weather Research and Forecasting model from 31 December 2009 through 3 January 2010. Model outputs were compared with extensive monitoring of meteorological data to examine the simulation ability. Model results between tests (with and without land-use change) show that the urbanization had major effects on meteorological fields across nearly the entire Pearl River Delta region and particularly in urban areas. Studied fields (wind speed, temperature, precipitation, and sensible and latent heat fluxes) were affected by the urbanization of the PRD region. The major influences occurred in urban areas, where wind speeds decreased greatly, while the daytime surface upward sensible heat flux clearly increased. Unlike the sensible heat flux, the latent heat flux had a nonmonotonic increase or decrease. As a consequence of the two heat fluxes, 2-m temperature varied with location and time. Change of precipitation was complex. The main rain band became more concentrated, while precipitation decreased upwind of the urban area and increased downwind.

High frequency surface wave radar (HFSWR) plays an important role in marine surveillance and target tracking. However, in the complex environment of interference, the ship target signals will be submerged, which lead to track breakage and miscorrelation. How to effectively detect and track specific targets continuously is the key problem to be solved in signal processing for HFSWR. In this paper, we propose a track matching method based on extreme learning machine (ELM). In this method, track features are fully explored: 1. Extract the key features of ship attributes based on track information; 2. Establish the matching relationship between track data and ship model based on ELM. The track matching accuracy is verified by both the simulation and field experiments, validating the effectiveness of the new method.

Our current understanding of how sugar metabolism affects inflammatory pathways in macrophages is incomplete. Here, we show that glycogen metabolism is an important event that controls macrophage-mediated inflammatory responses. IFN-γ/LPS treatment stimulates macrophages to synthesize glycogen, which is then channeled through glycogenolysis to generate G6P and further through the pentose phosphate pathway to yield abundant NADPH, ensuring high levels of reduced glutathione for inflammatory macrophage survival. Meanwhile, glycogen metabolism also increases UDPG levels and the receptor P2Y14 in macrophages. The UDPG/P2Y14 signaling pathway not only upregulates the expression of STAT1 via activating RARβ but also promotes STAT1 phosphorylation by downregulating phosphatase TC45. Blockade of this glycogen metabolic pathway disrupts acute inflammatory responses in multiple mouse models. Glycogen metabolism also regulates inflammatory responses in patients with sepsis. These findings show that glycogen metabolism in macrophages is an important regulator and indicate strategies that might be used to treat acute inflammatory diseases., Glycogen can be metabolized via glycogenolysis and the pentose phosphate pathway as well as into the production of UDP glucose, which when secreted can bind the P2Y14 receptor. Here the authors show how these glycogen metabolism pathways contribute to proinflammatory macrophage activation and susceptibility to sepsis.

Plant survival necessitates constant monitoring of fluctuating light and balancing growth demands with adaptive responses, tasks mediated via interconnected sensing and signaling networks. Photoreceptor phytochrome B (phyB) and plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) are evolutionarily conserved sensing and signaling components eliciting responses through unknown connection(s). Here, via a suppressor screen, we identify two phyB mutant alleles that revert the dwarf and high salicylic acid phenotypes of the high MEcPP containing mutant ceh1. Biochemical analyses show high phyB protein levels in MEcPP-accumulating plants resulting from reduced expression of phyB antagonists and decreased auxin levels. We show that auxin treatment negatively regulates phyB abundance. Additional studies identify CAMTA3, a MEcPP-activated calcium-dependent transcriptional regulator, as critical for maintaining phyB abundance. These studies provide insights into biological organization fundamentals whereby a signal from a single plastidial metabolite is transduced into an ensemble of regulatory networks controlling the abundance of phyB, positioning plastids at the information apex directing adaptive responses., MEcPP is an evolutionarily conserved metabolite that acts as a plastid-to-nucleus retrograde signal to regulate adaptive responses to fluctuating light. Here the authors show that MEcPP regulates seedling development by stabilizing the phyB photoreceptor in an auxin and Ca2+ dependent manner.

Cyclopropane fatty acids (CFAs) are synthetized by the addition of a methylene group from S-adenosyl-l-methionine across the carbon-carbon double bonds of unsaturated fatty acid chains of membrane phospholipids. This fatty acid cyclopropanation, catalyzed by the CFA synthase (CfaS) enzyme, occurs in many bacteria, including the human pathogen Helicobacter pylori. Although the cyclopropane modification was reported to play a key role in the adaptation in response to environmental stress, its role in H. pylori remains unknown. In this study, we showed that H. pylori HP0416 encodes a functional CfaS. The enzyme was demonstrated to be required for acid resistance, antibiotic resistance, intracellular survival and mouse gastric colonization, and cell membrane integrity. Moreover, the tool compound dioctylamine, which acts as a substrate mimic, directly inhibits the CfaS function of H. pylori, resulting into sensitivity to acid stress, increased antibiotic susceptibility, and attenuated abilities to avoid macrophage killing and to colonize mouse stomachs. These results validate CfaS as a promising antibiotic target and provide new potentials for this recognized target in future anti-H. pylori drug discovery efforts. IMPORTANCE The increasing prevalence of multidrug-resistant Helicobacter pylori strains has created an urgent need for alternative therapeutic regimens that complement the current antibiotic treatment strategies for H. pylori eradication; however, this is greatly hampered due to a lack of “druggable” targets. Although the CFAs are present in H. pylori cytoplasmic membranes at high levels, their physiological role has not been established. In this report, deletion of the CFA synthase CfaS was shown to attenuate acid and drug resistance, immune escape, and gastric colonization of H. pylori. These findings were validated by inhibition of the CfaS activity with the tool compound dioctylamine. These studies identify this enzyme as an attractive target for further drug discovery efforts against H. pylori.

Helicobacter pylori is a major global pathogen, and its infection represents a key factor in the etiology of various gastric diseases, including gastritis, peptic ulcers, and gastric carcinoma. The efficacy of current standard treatment for H. pylori infection including two broad-spectrum antibiotics is compromised by toxicity toward the gut microbiota and the development of drug resistance, which will likely only be resolved through novel and selective antibacterial strategies. Here, we synthesized a small molecule, zinc linolenate (ZnLla), and investigated its therapeutic potential for the treatment of H. pylori infection. ZnLla showed effective antibacterial activity against standard strains and drug-resistant clinical isolates of H. pylori in vitro with no development of resistance during continuous serial passaging. The mechanisms of ZnLla action against H. pylori involved the disruption of bacterial cell membranes and generation of reactive oxygen species. In mouse models of multidrug-resistant H. pylori infection, ZnLla showed in vivo killing efficacy comparable and superior to the triple therapy approach when use as a monotherapy and a combined therapy with omeprazole, respectively. Moreover, ZnLla treatment induces negligible toxicity against normal tissues and causes minimal effects on both the diversity and composition of the murine gut microbiota. Thus, the high degree of selectivity of ZnLla for H. pylori provides an attractive candidate for novel targeted anti-H. pylori treatment.

Uterine fibroids are common benign tumors in the female reproductive system. A hysterectomy is the most effective treatment for symptomatic fibroids. For patients desiring pregnancy, laparoscopic intracapsular myomectomy (LM) is an alternative surgery option. Although LM is widely accepted to treat fibroids, it is technically demanding with risk of excessive bleeding and difficult suturing, especially in cases with large fibroids or tumors in unusual locations. Therefore, we developed an intracapsular rotary-cut procedure (IRCP) as a modification of laparoscopic intracapsular myomectomy, with the intention to minimize risks of LM and help uterine healing. A summary of the improvements to the IRCP is described: 1) making an incision at the site of the fibroid with a length of one-third to one-half of the fibroid's diameter at a depth reaching the fibroid's surface; 2) holding the fibroid stably and making rotary cuts on the fibroid at a depth of 0.5-1 cm within its pseudo-capsule while pulling it outward slightly, making sure not to cut off any pieces of the fibroid; and 3) repeating the cutting-and-pulling until the longest dimension of the fibroid is outside the incision. The multiple cuts are to minimize the diameter and extend the length of the fibroid. When the multiple cuts cause half of the fibroid body to "shrink", the fibroid is squeezed out by contraction of the surrounding myometrium. Evaluation of the outcomes of IRCP showed that the time of enucleation and suturing, intraoperative bleeding, and decline of hemoglobin were significantly lower in the IRCP group than the LM group. As for reproductive outcomes, the full-term live birth rate of the IRCP group was significantly higher than that of LM group. However, there was no difference in delivery modes between the two groups. In conclusion, IRCP significantly benefits fertility preservation by minimizing damage to the uterus, protecting myofibers of the pseudo-capsule, and resulting in a shallower residual cavity, which eases stitching and causes less bleeding. It is worthwhile to adopt IRCP in younger patients who desire preservation of their fertility.

Background Staphylococcal enterotoxin A (SEA) is a well-known superantigen and stimulates human peripheral blood mononuclear cells (PBMCs) involving in the pathogenesis of inflammatory disorders and cancer. Objective To better understand the biological activities of SEA and the possible intracellular mechanisms by which SEA plays its roles in conditions like staphylococcal inflammatory and/or autoimmune disorders and immunotherapy. Methods Recombinant SEA (rSEA) was expressed in a prokaryotic expression system and its effects on the cytokine and chemokine production was examined by Enzyme-linked Immunospot (ELISpot) Assay and ELISA analysis. Results In vitro experiments showed rSEA could significantly enhance secretion of a broad spectrum of cytokines and chemokines from PBMCs dose-dependently. Increased secretion of cytokines and chemokines from rSEA stimulated PBMCs was barely affected by C-C motif chemokine receptor 2 (CCR2) antagonist INCB3344. However, Src, ERK and STAT pathway inhibitors were able to successfully block the enhanced secretion of most of cytokines and chemokines produced by rSEA stimulated PBMCs. Conclusions Our work suggested that rSEA serves as a potent stimulant of PBMCs, and induces the release of cytokines and chemokines through Src, ERK and STAT pathways upon a relatively independent network. Our work also strongly supported that Src, ERK and STAT signaling inhibitors could be effective therapeutic agents against diseases like toxic shock syndrome or infection by microbes resistant to antibiotics.

RNA silencing (RNAi) has a well-established role in anti-viral immunity in plants. The destructive eukaryotic pathogen Phytophthora encodes suppressors of RNAi (PSRs), which enhance plant susceptibility. However, the role of small RNAs in defense against eukaryotic pathogens is unclear. Here, we show that Phytophthora infection of Arabidopsis leads to increased production of a diverse pool of secondary small interfering RNAs (siRNAs). Instead of regulating endogenous plant genes, these siRNAs are found in extracellular vesicles and likely silence target genes in Phytophthora during natural infection. Introduction of a plant siRNA in Phytophthora leads to developmental deficiency and abolishes virulence, while Arabidopsis mutants defective in secondary siRNA biogenesis are hypersusceptible. Notably, Phytophthora effector PSR2 specifically inhibits secondary siRNA biogenesis in Arabidopsis and promotes infection. These findings uncover the role of siRNAs as antimicrobial agents against eukaryotic pathogens and highlight a defense/counter-defense arms race centered on trans-kingdom gene silencing between hosts and pathogens.

Background: Recurrent and intractable chronic itch is a world-wide problem but mechanisms, especially the neural mechanisms, underlying chronic itch still remain unclear. In this study, we investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis induced by squaric acid dibutylester (SADBE). Methods: Behavioral tests in combination to genetic, pharmacological, neurotoxic approaches were performed on mouse models. Immunohistochemistry, RNAscope in situ hybridization assay, quantitative RT-PCR, multiplex Luminex assay and western blot were performed using mouse tissues. Western blot analysis also performed using transfected HEK293T cells as well. Findings: We found that repeated exposure of mice to SADBE evoked persistent spontaneous scratching lasting for weeks. SADBE-induced prolonged itch requires both histaminergic and nonhistaminergic pathways and is relayed by gastrin-releasing peptide receptor (GRPR) and natriuretic peptide receptor A (NPRA) in the spinal cord. We showed sustained extracellular signal-regulated kinase phosphorylation (pERK) in the spinal cord and its importance for prolonged itch. Both in vivo and in vitro analysis demonstrated that ERK is the primary downstream pathway of spinal itch receptors like GRPR, NPRA, somatostatin receptor sst2A and Neuromedin B receptor (NMBR). Interpretation: In spinal cord neural circuits, ERK activation exhibits considerable heterogeneity but plays a central role for chronic itch. Funding Statement: This work was supported by the National Natural Science Foundation of China under Grants 81301948, the National Science and Technology Major Project of China (2016ZX08011-005) and the Guangzhou science and technology project (201804020042). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All animal experiments were performed under protocols approved by the Animal Studies Committee of Guangzhou Medical University.

As a green industry, tourism provides a new path for the green development of rural areas and plays an important role in the development of rural economy and the construction of ecological civilization, the sustainable participation willingness of the practitioners is the primary factor that affects the sustainable development of rural tourism. This paper studies the effect of Social Interaction on sustainable participation of practitioners. Through the empirical analysis, it is found that the interaction between practitioners and tourists, government and neighbours has a significant positive impact on the willingness of practitioners to continue to participate in rural tourism. Practitioners’ satisfaction with local tourism development plays an intermediary role in social interaction behaviour and willingness to participate continuously.

Intravenous leiomyomatosis is a rare benign disease. We here in present the case of a 39-year-old woman with a history of hysterectomy who presented with intermittent abdominal pain, palpitations and tightness of the chest. Physical examination revealed the presence of a pelvic mass of regular shape. Gynecological ultrasonography, computed tomography scans and three-dimensional (3D) cardiac ultrasonography were used to evaluate the imaging characteristics of the mass and reach a final diagnosis. The mass appeared to extend to the iliac veins, renal veins and inferior vena cava on imaging examination. The mass was successfully excised under non-extracorporeal circulation in one stage. Pathological examination of tumor samples indicated intravenous leiomyomatosis. After the operation, the symptoms were dissipated and no abnormal echo was observed in the inferior vena cava or the right atrium on 3D-cardiac ultrasonography. The patient is currently followed up without signs of recurrence. The aim of the present study was to describe in detail the diagnostic procedure and treatment in order to improve our current understanding of this disease.

Gene duplication allows for functional divergence and innovation that provide selective advantages. However, in flowering plants genetic studies have revealed that single-gene mutations affecting one of two or more closely related paralogs often fail to cause detectable morphological defects, suggesting functional redundancy. Flowering plants have hundreds of genes encoding leucine-rich repeat receptor-like protein kinases (LRR-RLKs), several of which play important roles in anther development, but little is known about their evolutionary history and possible functional divergence. We investigated the evolutionary relationship of the LRR-RLK gene family by phylogenetic analysis and found that these closely related paralogs resulted from multiple duplication events, such as the one resulting in BAM1 and BAM2. We further used quantitative real-time reverse transcription–polymerase chain reaction to verify gene expression changes in immature anthers from the bam1/bam2 single and double mutants compared with wild type, providing strong evidence that the BAM1 and BAM2 genes have evolved different functions, with differential effects on anther gene expression. Moreover, careful examination of anther development in bam1 and bam2 single mutants revealed previously unrecognized extra cell division in tapetum cell layers. Thus our results from phylogenetic, molecular, and morphological analyses uncover sequence and functional differences between paralogs whose single mutants lack obvious fertility defects, effectively revealing functional divergence of duplicate genes.

Chemotherapy can lead to the loss of fertility and premature ovarian failure in young women who suffer from malignant diseases. Freezing ovarian tissue by vitrification allows for the preservation of a large number of follicles prior to treatment, yet no established protocols have been optimized with respect to the vitrification solution. The aim of the present study was to evaluate the early stage of human ovarian tissue xenotransplantated onto the chick embryo chorioallantoic membrane after vitrification, and to determine the effect of different vitrification solutions on ovarian tissue quality-as defined by morphology and viability of follicles, neovascularization, cell proliferation, and apoptosis. Each vitrification protocol had a different impact on ovarian tissue at the early transplantation stage; one process using the lowest concentrations of ethylene glycol and dimethylsulfoxide, plus sucrose, demonstrated a moderate advantage compared to the other protocols. We also demonstrated that the chorioallantoic membrane model can be a useful alternative for short-term xenotransplantation studies of angiogenesis into human ovarian cortical tissue.

Recurrent and intractable chronic itch is a worldwide problem, but mechanisms, especially the neural mechanisms, underlying chronic itch still remain unclear. In this study, we investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis induced by squaric acid dibutylester. We found that repeated exposure of mice to squaric acid dibutylester evoked persistent spontaneous scratching and significantly aberrant cutaneous and systemic immune responses lasting for weeks. Squaric acid dibutylester–induced itch requires both nonhistaminergic and histaminergic pathways, which are likely relayed by GRPR and NPRA in the spinal cord, respectively. Employing genetic, pharmacologic, RNAscope assay, and cell-specific ablation methods, we dissected a neural circuit for prolonged itch formed as Grpr+ neurons act downstream of Npr1+ neurons in the spinal cord. Taken together, our data suggested that targeting GRPR and NPRA may provide effective treatments for allergic contact dermatitis–associated chronic pruritus.

Isomorphism identification of kinematic chains occupies an important place in the field of mechanism structure synthesis. A method to identify the isomorphism of multistage planetary gear trains is proposed in this paper. Firstly, the structure topology model and the corresponding link-link adjacency matrix are presented, to describe the schematic diagram of multistage planetary gear trains. Then, based on the hamming number method, the hamming number matrix is obtained by the link-link adjacency matrix, and the hamming value of link, the hamming number and the hamming strings of multistage planetary gear trains are introduced, which can determine whether the multistage planetary gear trains is isomorphic or not. The study shows that this work is beneficial to the development of new multistage planetary gear trains.

Angiosperms (flowering plants) are the most diverse and species-rich group of plants. The vast majority (∼99.95%) of angiosperms form a clade called Mesangiospermae, which is subdivided into five major groups: eudicots, monocots, magnoliids, Chloranthales, and Ceratophyllales. The relationships among these Mesangiospermae groups have been the subject of long debate. In this study, we assembled a phylogenomic dataset of 1594 genes from 151 angiosperm taxa, including representatives of all five lineages, to investigate the phylogeny of major angiosperm lineages under both coalescent- and concatenation-based methods. We dissected the phylogenetic signal and found that more than half of the genes lack phylogenetic information for the backbone of angiosperm phylogeny. We further removed the genes with weak phylogenetic signal and showed that eudicots, Ceratophyllales, and Chloranthales form a clade, with magnoliids and monocots being the next successive sister lineages. Similar frequencies of gene tree conflict are suggestive of incomplete lineage sorting along the backbone of the angiosperm phylogeny. Our analyses suggest that a fully bifurcating species tree may not be the best way to represent the early radiation of angiosperms. Meanwhile, we inferred that the crown-group angiosperms originated approximately between 255.1 and 222.2 million years ago, and Mesangiospermae diversified into the five extant groups in a short time span (∼27 million years) at the Early to Late Jurassic., Angiosperms (flowering plants) are the most diverse and species-rich group of plants. The relationships among the early divergent lineages of angiosperms have been the subject of long debate. By assembling a phylogenomic dataset of 1594 genes from 151 angiosperm taxa, this study investigates the angiosperm phylogeny and reveals that a fully bifurcating species tree may not be the best way to represent the early radiation of angiosperms.

A fuzzy PI speed controller based on fuzzy control theory is proposed, which makes the drive control system of electric vehicle insensitive to disturbance and parameter change. The mathematical model of permanent magnet synchronous motor (PMSM) in d-q reference frame is established, fuzzy PI speed controller is designed based on fuzzy control theory, and simulation models of PMSM based on fuzzy PI control theory and sliding mode control theory are built in this paper. Two simulation models are simulated and analysed by Simulink, and simulation result shows that fuzzy PI control has faster dynamic response speed, better dynamic performance and better antiinterference ability than sliding mode control. Therefore, fuzzy PI control is an ideal control method, which has a certain reference value in vector control of PMSM for electric vehicle.

Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, controls the formation and maintenance of CD8

Background Flowering time is a key trait for regional adaption and seed production in rice (Oryza sativa L.). Forward and reverse genetic studies have characterized a number of flowering-time genes. However, co-expression analysis has not been used to identify the flowering-time genes. Results We predicted a G2-like family transcription factor, OsPHL3, by co-expression networks analysis with photoperiodic flowering pathway genes. OsPHL3 contains a MYB-CC domain, and was localized in the nucleus with transcriptional activation potential. OsPHL3 was mainly expressed in the leaves and exhibited a circadian rhythmic expression pattern. Rice lines overexpressing OsPHL3 showed a delayed flowering time in the genetic background of TP309 under both long-day (Beijing) and short-day (Hainan) conditions. By contrast, the knockout rice lines of OsPHL3 by CRISPR/Cas9 technology promoted flowering time regardless of genetic backgrounds (i.e. Nipponbare and TP309) or day length. Further analysis indicated that OsPHL3 delayed flowering time by down-regulating the expression of Hd3a and RFT1 through promoting Hd1 under long-day conditions (LDs), or suppressing Ehd1/Hd1 under short-day conditions (SDs). Conclusions Our results suggested that co-expression analysis is a useful strategy for identifying novel flowering-time genes in rice. Electronic supplementary material The online version of this article (10.1186/s12870-018-1382-6) contains supplementary material, which is available to authorized users.

The goal of diabetic drug treatment is to stabilize the blood sugar for a long time to close to the normal level, to correct the metabolic disorder and eliminate the symptoms. At present, glimepiride has become commonly used drugs for the treatment of diabetes with obesity. Compared with metformin, acarbose and rosiglitazone, glimepiride has different mechanisms of drug action, clinical combination showed synergistic hypoglycemic effect, good clinical curative effect. So, we use three treatments to study as group A (glimepiride and metformin); group B (glimepiride and acarbose); Group C (glimepiride and rosiglitazone). From the analysis of drug economics, glimepiride and metformin scheme is better, has the lowest cost per unit cost effect. From the comparison of scheme is efficient, the best curative effect is rosiglitazone plus glimepiride, effective rate as 96.7%. At the same time, the drug can be rationally used to reduce the occurrence of some drug-induced diseases and adverse drug reactions.

The citrus industry is facing an unprecedented challenge from Huanglongbing (HLB). All cultivars can be affected by the HLB-associated bacterium ‘Candidatus Liberibacter asiaticus’ (CLas) and there is no known resistance. Insight into HLB pathogenesis is urgently needed in order to develop effective management strategies. Here, we use Sec-delivered effector 1 (SDE1), which is conserved in all CLas isolates, as a molecular probe to understand CLas virulence. We show that SDE1 directly interacts with citrus papain-like cysteine proteases (PLCPs) and inhibits protease activity. PLCPs are defense-inducible and exhibit increased protein accumulation in CLas-infected trees, suggesting a role in citrus defense responses. We analyzed PLCP activity in field samples, revealing specific members that increase in abundance but remain unchanged in activity during infection. SDE1-expressing transgenic citrus also exhibit reduced PLCP activity. These data demonstrate that SDE1 inhibits citrus PLCPs, which are immune-related proteases that enhance defense responses in plants., Greening disease threatens the productivity of citrus crops worldwide yet the pathosystem is poorly understood. Here, Clark et al. show that an effector cloned from the associated bacteria can suppress host plant papain-like cysteine proteases' activity, suggesting its probable role in pathogenesis.

Antifungal treatment is often ineffectual, partly because of biofilm formation. In this study, by using a combined forward and reverse genetic strategy, we identified that nucleus-localized AfSsn3 and its partner AfSsn8, which constitute a Cdk8-cyclin pair, are required for azole resistance in Aspergillus fumigatus . Deletion of Afssn3 led to increased absorption and utilization of glucose and amino acids. Interestingly, absorption and utilization of glucose accelerated the extracellular polysaccharide formation, while utilization of the amino acids serine, threonine, and glycine increased sphingolipid pathway intermediate accumulation. In addition, the absence of Afssn3 induced the activity of the efflux pump proteins. These factors indicate the mature biofilm is responsible for the major mechanisms of A. fumigatus resistance to azoles in the Δ Afssn3 mutant. Collectively, the loss of Afssn3 led to two “barrier” layers between the intracellular and extracellular spaces, which consequently decreased drug penetration into the cell.

Table S2. The sequence of primers used in this study. (DOCX 13 kb)

Background: The human uterus is traditionally believed to be sterile, while the vaginal microbiota plays an important role in fending off pathogens. Emerging evidence demonstrates the presence of bacteria beyond the vagina. However, a microbiome-wide metagenomic analysis characterizing the diverse microbial communities has been lacking.Results: We performed shotgun-sequencing of 52 samples from the cervical canal and the peritoneal fluid of Chinese women of reproductive age using the Illumina platform. Direct annotation of sequencing reads identified the taxonomy of bacteria, archaea, fungi and viruses, confirming and extending the results from our previous study. We replicated our previous findings in another 24 samples from the vagina, the cervical canal, the uterus and the peritoneal fluid using the BGISEQ-500 platform revealing that microorganisms in the samples from the same individuals were largely shared in the entire reproductive tract. Human sequences made up more than 99% of the 20GB raw data. After filtering, vaginal microorganisms were well covered in the generated reproductive tract gene catalogue, while the more diverse upper reproductive tract microbiota would require greater depth of sequencing and more samples to meet the full coverage scale.Conclusions: We provide novel detailed data on the microbial composition of a largely unchartered body site, the female reproductive tract. Our results indicated the presence of an intra-individual continuum of microorganisms that gradually changed from the vagina to the peritoneal fluid. This study also provides a framework for understanding the implications of the composition and functional potential of the distinct microbial ecosystems of the female reproductive tract in relation to health and disease.

Plants have evolved a large number of transcription factors (TF), which are enriched among duplicate genes, highlighting their roles in complex regulatory networks. The APETALA2/EREBP-like genes constitute a large plant TF family and participate in development and stress responses. To probe the conservation and divergence of AP2/EREBP genes, we analyzed the duplication patterns of this family in Brassicaceae and identified interacting proteins of representative Arabidopsis AP2/EREBP proteins. We found that many AP2/EREBP duplicates generated early in Brassicaceae history were quickly lost, but many others were retained in all tested Brassicaceae species, suggesting early functional divergence followed by persistent conservation. In addition, the sequences of the AP2 domain and exon numbers were highly conserved in rosids. Furthermore, we used 16 A. thaliana AP2/EREBP proteins as baits in yeast screens and identified 1,970 potential AP2/EREBP-interacting proteins, with a small subset of interactions verified in planta. Many AP2 genes also exhibit reduced expression in an anther-defective mutant, providing a possible link to developmental regulation. The putative AP2-interacting proteins participate in many functions in development and stress responses, including photomorphogenesis, flower development, pathogenesis, drought and cold responses, abscisic acid and auxin signaling. Our results present the AP2/EREBP evolution patterns in Brassicaceae, and support a proposed interaction network of AP2/EREBP proteins and their putative interacting proteins for further study.