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ZFP91 positively regulates IL-1β production in macrophages and may be a potential therapeutic target to treat inflammatory-related diseases. We investigated whether this process is modulated by convallatoxin, which is a cardiac glycoside isolated from the traditional Chinese medicinal plant Adonis amurensis Regel et Radde.In vitro, the mechanisms by which convallatoxin inhibits ZFP91-regulated IL-1β expression were investigated using molecular docking, western blotting, RT-PCR, ELISA, immunofluorescence and immunoprecipitation assays.In vivo, mice liver injury was induced by an intraperitoneal injection of D-GalN and LPS, colitis was induced by oral administration of dextran sulfate sodium (DSS) in drinking water and peritonitis was induced by an intraperitoneal injection of alum.We confirmed that convallatoxin inhibited the release of IL-1β by down-regulating ZFP91. Importantly, we found that convallatoxin significantly reduced K63-linked polyubiquitination of pro-IL-1β regulated by ZFP91 and decreased the efficacy of pro-IL-1β cleavage. Moreover, convallatoxin suppressed ZFP91-mediated activation of the non-canonical cysteine-requiring aspartate protease-8 (caspase-8) inflammasome and MAPK signalling pathways in macrophages. Furthermore, we showed that ZFP91 promoted the assembly of the caspase-8 inflammasome complex, whereas convallatoxin treatment reversed this result. Mice in vivo studies further demonstrated that convallatoxin ameliorated D-GalN/LPS-induced liver injury, DSS-induced colitis and alum-induced peritonitis by down-regulating ZFP91.We show for the first time that convallatoxin-mediated inhibition of ZFP91 is an important regulatory event that prevents inappropriate inflammatory responses to maintain immune homeostasis. This mechanism provides new insight for the development of convallatoxin as a novel anti-inflammatory drug targeting ZFP91.This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.

A novel Multiple Context Learning Network (MCLN) is proposed to model multiple contexts for visual question answering (VQA), aiming to learn comprehensive contexts. Three kinds of contexts are discussed and the corresponding three context learning modules are proposed based on a uniform context learning strategy. Specifically, the proposed context learning modules are visual context learning module (VCL), textual context learning module (TCL), and visual-textual context learning module (VTCL). The VCL and TCL, respectively, learn the context of objects in an image and the context of words in a question, allowing object and word features to own intra-modal context information. The VTCL is performed on the concatenated visual-textual features that endows the output features with synergic visual-textual context information. These modules work together to form a multiple context learning layer (MCL) and MCL can be stacked in depth for deep context learning. Furthermore, a contextualized text encoder based on the pretrained BERT is introduced and fine-tuned, which enhances the textual context learning at the feature extraction stage of text. The approach is evaluated by using two benchmark datasets: VQA v2.0 dataset and GQA dataset. The MCLN achieves 71.05% and 71.48% overall accuracy on the test-dev and test-std sets of VQA v2.0, respectively. And an accuracy of 57.0% is gained by the MCLN on the test-standard split of GQA dataset. The MCLN outperforms the previous state-of-the-art models and the extensive ablation studies examine the effectiveness of the proposed method.

BACKGROUND: Epidemiological studies on the relationship between dietary glycemic index (GI), glycemic load (GL) and all-cause and cause-specific mortality yielded conflict results. We aimed to assess these associations in Chinese. METHODS: We conducted this study based on two prospective cohort studies in Shanghai. Dietary information was collected using validated cohort-specific food frequency questionnaires. We used Cox regression model to estimate the hazard ratios (HR) for mortality associated with GI and GL. RESULTS: After median follow-up periods of 12.8 years for 59,770 men and 18.2 years for 74,735 women, 8,711 deaths in men and 10,501 deaths in women were documented. After we controlled the potential confounders, dietary GI, GL, and carbohydrate intake were associated with a higher risk of cardiovascular disease (CVD) mortality (P values for trend = 0.025, 0.001, and 0.001). Dietary GI was associated with lower risk of total and cause-specific mortality in men in the second quartile (Q) (all-cause mortality: HR(Q2 vs. Q1) = 0.89, 95%CI: 0.84, 0.95). Dietary GL was associated with mortality due to lower risk of cancer but higher risk of CVD mortality in men. In women, dietary GI was associated with mortality due to all-cause (HR(Max Q4 vs. Q1) = 1.10, 95%CI: 1.04, 1.06), cancer (HR(Max Q4 vs. Q1) = 1.12, 95%CI: 1.02, 1.23), and CVD (HR(Max Q4 vs. Q1) = 1.10, 95%CI: 1.00, 1.22). CONCLUSIONS: The present study indicates that diet with higher GI and GL was associated with an increased risk of CVD mortality in Chinese adults. The association may vary for men and women, which need further investigating in other Asian populations.

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Citrus sinensis is the most cultivated and economically valuable Citrus species in the world, whose genome has been assembled by three generation sequencing. However, chromosome recognition remains a problem due to the small size of chromosomes, and difficulty in differentiating between pseudo and real chromosomes because of a highly heterozygous genome. We employed fluorescence in situ hybridization (FISH) with nine chromosome painting probes, thirty oligo pools and eight repetitive sequences to visualize 18 chromosomes. Then we developed an approach to identify each chromosome in one cell through single experiment of oligo-FISH and Chromoycin A3 (CMA) staining. By this approach, we constructed a high-resolution molecular cytogenetic map containing the physical positions of CMA banding and 38 sequences of FISH including centromere regions, which enable us to visualize significant differences between homologous chromosomes. Based on the map, we located several highly repetitive sequences on chromosomes, and estimated sizes and copy numbers of each site. In particular, we discovered the translocation regions of chromosomes 4 and 9 in C. sinensis 'Valencia'. The high-resolution molecular cytogenetic map will help improve understanding of sweet orange genome assembly and also provide a fundamental reference for investigating chromosome evolution and chromosome engineering for genetic improvement in Citrus.

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Substituted thioureas with 1,3-thiazole and d-glucose were gained from 2-amino-1,3-thiazoles and glucopyranosyl isocyanate. They had antimicrobial activity, some inhibiting S. aureus DNA gyrase, DNA Topo IV, and dihydrofolate reductase. IFD, MM-GBSA and MD were performed.

A method to suppress cross-band scattering is presented in this letter. A two-antenna system is analyzed, which consists of a lower-band (LB) dipole and a higher-band (HB) dipole. A pair of sleeves is loaded on the arms of the LB dipole. The cross-band scattering between the HB and LB antennas close to each other usually deteriorates the pattern of the HB antenna. In the proposed antenna system, the sleeves loaded on the arms of the LB dipole are used to suppress the induced current on the LB antenna and reduce the cross-band scattering in the two-dipole system, which restores the radiation pattern of the HB antenna. A prototype of the proposed antenna system is fabricated and measured. The results show that the maximum radiation direction of the HB antenna is changed from a maximum of 24 degrees back to 0 degrees in H-plane.

Purpose: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) is a heterogeneous group of tumors with histological and biological diversity that cannot be defined as a benign leiomyoma or malignant leiomyosarcoma. The study aims to investigate the diagnostic methods, treatment management and prognosis of STUMP patients in a 13-year period. Methods: We retrospectively reviewed the clinicopathologic information of 31 STUMP patients in Peking University People’s Hospital. Statistical analyses were conducted to compare the difference of clinical characteristics between the women in myomectomy group and those in hysterectomy group. Results: The most common clinical presentation was menstrual disorder. The tumors were mainly manifested as hypoechoic, non-cystic nodules with low blood flow signal by pelvic doppler ultrasonography. Most tumors carried Ki-67 index ranging from 10% to 30%. Immunohistochemical markers such as ER, PR, p16 and Desmin was positively expressed in tumors. At the first operation, 21 cases underwent myomectomy and 10 cases underwent hysterectomy. The patients in myomectomy group were younger than those in hysterectomy group. In the follow-up period, two cases experienced a relapse in the form of STUMP within 36 months. One case died of cardiovascular accident while the other cases were alive. Six of 21 women in myomectomy group desired pregnancy and two healthy live births were recorded.Conclusion: The diagnosis of STUMP primarily depends on histopathologic features. Fertility-sparing surgery may be a treatment selection for patients with fertility desire. Patients with STUMP, especially in the case of myomectomy, should be informed of recurrence risk and monitored closely.

Immune checkpoint inhibitors (ICIs) have shown encouraging outcomes against Lynch syndrome (LS)-associated colorectal cancer (CRC) and endometrial cancer with mismatch repair deficient/microsatellite instability–high (dMMR/MSI-H). However, there is as yet no clarity on the safety and efficacy of immunotherapy combined with chemotherapy in LS-associated urothelial carcinoma (UC). Here, we report a patient with recurrent and metastatic LS-associated UC who achieved sustained response to programmed death protein 1 (PD-1) inhibitor combined with chemotherapy over 31 months, during which the side effects of immunotherapy could be controlled and managed. Our findings indicate that the dMMR/MSI status and PD-1 expression in UC may have potential predictive value for the response to PD-1-targeted immunotherapy. Our case supports the inclusion of such combination and/or monotherapy for UC in clinical studies and using dMMR/MSI status and PD-1 expression as potential predictive biomarkers for assessment of the therapeutic response.

Population-based prospective studies on the associations of cigarette smoking, alcohol drinking, and primary liver cancer remain limited in Mainland China. Our study was designed to evaluate such relationships in middle-aged Chinese men.Self-reported habits of cigarette smoking and alcohol drinking were obtained from all cohort members at the baseline survey. The outcomes were identified through in-person follow-up and annual record linkage to multiple statistics of vital and cancer registration. Age-adjusted and multivariable-adjusted hazard ratio (HR) and their corresponding 95% confidence interval (CI) were estimated utilizing the Cox regression model.After a median follow-up of 12.31 years, 329 cases of incident primary liver cancer occurred among 45 266 male participants. Compared with never smoker, former smoker was positively associated with liver cancer risk, with a multivariable-adjusted HR of 1.42 (95% CI 1.02-1.98). Individuals who had smoked for more than 40 years had a 49% increased risk of liver cancer (HROur study provided evidence that cigarette smoking was positively associated with an increased liver cancer risk among Chinese men. Attention to such non-viral modifiable risk factors to prevent liver cancer effectively is needed.

Prospective epidemiological studies have provided limited evidence for an association between tea consumption and liver cancer risk. Based on a population-based prospective cohort study in middle-aged Chinese women, we investigated the association between tea consumption and the risk of primary liver cancer. Detailed information on tea drinking habits and other potential confounders was obtained at the baseline interview. Incident liver cancer cases were identified through record linkage with the population-based cancer registry and verified through home visits and review of medical charts by medical experts. Multiple aspects of tea drinking habits including starting age, duration, intensity and cumulative consumption of any type of tea and green tea were considered. Multivariable-adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) were derived from the Cox regression models. After a median follow-up time of 18.12 (interquartile range = 1.59) years, 253 incident liver cancer cases were identified from 71 841 cohort members. Compared with never tea drinkers, the risk of liver cancer for participants who have consumed over 30 kg of dried tea leaves cumulatively was 0.56 (95% CI: 0.32-0.97). For those who drank green tea only, the aHR was 0.54 (95% CI: 0.30-0.98). This updated study suggested an inverse association between cumulative consumption of tea, especially green tea and the risk of primary liver cancer.

The syncytiotrophoblast, derived from cytotrophoblast fusion, is responsible for maternal–fetal exchanges, secretion of pregnancy-related hormones, and fetal defense against pathogens. Inadequate cytotrophoblast fusion can lead to pregnancy disorders, such as preeclampsia and fetal growth restriction. However, little is known about the mechanism of cytotrophoblast fusion in both physiological and pathological pregnancy conditions. In this study, P57kip2 (P57), a cell cycle-dependent kinase inhibitor that negatively regulates the cell cycle, was found to be up-regulated during the process of syncytialization in both primary trophoblast cells and BeWo cells. Co-immunofluorescence with proliferation markers Ki67 and Cyclin-CDK factors further showed that P57 specifically localizes in the post-mitotic cytotrophoblast subtype of the early pregnancy villi. Overexpression of P57 promoted trophoblast syncytialization by arresting the cell cycle at the G1/G0 phase and inhibiting proliferation. Blocking of the cell cycle through a serum starvation culture resulted in an enhancement of cytotrophoblast fusion and the up-regulation of P57. In both spontaneous cytotrophoblast fusion and forskolin-induced BeWo cell fusion models, an initial up-regulation of P57 was observed followed by a subsequent down-regulation. These findings indicate that proper expression of P57 at cytotrophoblast differentiation nodes plays an important role in trophoblast syncytialization.

Objective To investigate current autologous transplantation methods and sites of ovarian tissues in sheep. Methods Sheep ovaries were resected. Ovarian cortices were sliced and transplanted orthotopically into the ovarian mesangial latum and heterotopically into the greater omentum and under groin skin. The grafts were removed two months after transplantation and examined to evaluate the survival of follicles (hematoxylin-eosin staining) and help determining feasible graft sites and transplantation methods. Results Graft nodules were found in the transplanted sites. HE staining of the grafts showed that multiple primordial follicles were able to survive in the grafts on both sides of the ovarian mesangial latum, the right side of the greater omentum, and the left inguinal subcutaneous tissue. Secondary or cystic follicles were found in almost all of the grafts. Conclusion The ovarian mesangial latum, the greater omentum and the inguinal subcutaneous tissue can be used as autologous transplantation sites, where sheep ovarian tissue can survive and the follicles grow and develop in good condition.