18F-FDG PET/CT characterization and response evaluation in a case of lymphomatoid granulomatosis involving the main pulmonary artery.

Main pulmonary artery (MPA) involvement of lymphomatoid granulomatosis (LYG) is extremely rare. We described fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings in a case with LYG originated from the MPA. Fluorine-18-FDG PET/CT demonstrated nodular hypermetabolic foci in the MPA, corresponding well to the intraluminal filling defects on CT pulmonary angiography, and the secondary right heart dysfunction was observed. Final diagnosis was made after transcatheter MPA biopsies and multi-disciplinary consultation. The patient recovered completely following the steroid therapy and MPA stenting, which was illustrated on the second 18F-FDG PET/CT.

Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions.

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 µg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.

Identification and Validation of Reference Genes for qRT-PCR Analysis of Petal-Color-Related Genes in Rosa praelucens.

The flower's color is regarded as one of the most outstanding features of the rose. Rosa praelucens Byhouwer, an endemic and critically endangered decaploid wild rose species, is abundant in phenotypic diversity, especially in flower color variation, from white to different degrees of pink. The mechanism underlying this variation, e.g., the level of petal-color-related genes, is worth probing. Seven candidate reference genes for qRT-PCR analysis, including tubulin α chain (TUBA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histone H2B (Histone2A), eukaryotic translation elongation factor 1-α (EEF1A), 60S ribosomal protein (RPL37), eukaryotic translation initiation factor 1-α (EIF1A), and aquaporins (AQP), were detected from the transcriptome datasets of full blooming flowers of white-petaled and pink-petaled individuals, and their expression stabilities were evaluated through qRT-PCR analysis. According to stability rankings analysis, EEF1A showed the highest stability and could be chosen as the most suitable reference gene. Moreover, the reliability of EEF1A was demonstrated via qRT-PCR analysis of six petal-color-related target genes, the expression patterns of which, through EEF1A normalization, were found to be consistent with the findings of transcriptome analysis. The result provides an optimal reference gene for exploring the expression level of petal-color-related genes in R. praelucens, which will accelerate the dissection of petal-color-variation mechanisms in R. praelucens.

Effects of short- and long-term plant functional group loss on alpine meadow community structure and soil nutrients.

The rapid loss of global biodiversity can greatly affect the normal functioning of ecosystems. However, how biodiversity losses affect plant community structure and soil nutrients is unclear. We conducted a field experiment to examine the short- and long-term effects of removing plant functional groups (Gramineae, Cyperaceae, legumes, and forbs) on the interrelationships among the species diversity, productivity, community structure, and soil nutrients in an alpine meadow ecosystem at Menyuan County, Qinghai Province. The variations in the species richness, above- and belowground biomass of the community gradually decreased over time. Species richness and productivity were positively correlated, and this correlation tended to be increasingly significant over time. Removal of the Cyperaceae, legumes, and other forbs resulted in fewer Gramineae species in the community. Soil total nitrogen, phosphorus, organic matter, and moisture contents increased significantly in the legume removal treatment. The removal of other forbs led to the lowest negative cohesion values, suggesting that this community may have difficulty recovering its previous equilibrium state within a short time. The effects of species removal on the ecosystem were likely influenced by the species structure and composition within the community. Changes in the number of Gramineae species indicated that they were more sensitive and less resistant to plant functional group removal. Legume removal may also indirectly cause distinct community responses through starvation and compensation effects. In summary, species loss at the community level led to extensive species niche shifts, which caused community resource redistribution and significant changes in community structure.

Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. METHODS: We conducted an investigator-initiated, multicentre, open-label, randomised controlled trial in ten reproductive medicine centres across China. Couples with infertility with non-severe male factor without a history of poor fertilisation were randomly assigned (1:1) to undergo either ICSI or conventional IVF. The primary outcome was live birth after first embryo transfer. We performed the primary analysis in the intention-to-treat population using log-binomial regression models for categorical outcomes or linear regression models for continuous outcomes, adjusting for centre. This trial is registered with Clinicaltrials.gov, NCT03298633, and is completed. FINDINGS: Between April 4, 2018, and Nov 15, 2021, 3879 couples were screened, of whom 2387 (61·5%) couples were randomly assigned (1184 [49·6%] to the ICSI group and 1203 [50·4%] to the conventional IVF group). After excluding couples who were ineligible, randomised twice, or withdrew consent, 1154 (97·5%) in the ICSI group and 1175 (97·7%) in the conventional IVF group were included in the primary analysis. Live birth after first embryo transfer occurred in 390 (33·8%) couples in the ICSI group and in 430 (36·6%) couples in the conventional IVF group (adjusted risk ratio [RR] 0·92 [95% CI 0·83-1·03]; p=0·16). Two (0·2%) neonatal deaths were reported in the ICSI group and one (0·1%) in the conventional IVF group. INTERPRETATION: In couples with infertility with non-severe male factor, ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Beijing Municipal Science & Technology Commission, and Peking University Third Hospital.

Indigofera suffruticosa aerial parts extract induce G2/M arrest and ATR/CHK1 pathway in Jurkat cells.

BACKGROUND: Indigofera suffruticosa Mill. is used as a folk medicine for treating patients with leukemia, however very little is known regarding the molecular mechanism of its anti-leukemic activity and the chemical profile of the active extract. The present study aimed to reveal the molecular effect of I. suffruticosa aerial parts extract (ISAE) on leukemia cells and its chemical constituents. METHODS: Cytotoxicity of ISAE were determined by resazurin viability assay, multitox - Glo multiplex cytotoxicity assay, and Annexin V staining assay. Cell cycle profiles were revealed by propidium iodide staining assay. The effects of ISAE on G2/M arrest signaling and DNA damage were evaluated by Western blot assay and phospho-H2A.X staining assay. The chemical profile of ISAE were determined by tandem mass spectroscopy and molecular networking approach. RESULTS: We showed that the acute lymphoblastic leukemia cell line Jurkat cell was more responsive to ISAE treatment than other leukemia cell lines. In contrast, ISAE did not induce cytotoxic effects in normal fibroblast cells. Cell cycle analysis revealed that ISAE triggered G2/M arrest in Jurkat cells in dose- and time-dependent manners. Elevation of annexin V-stained cells and caspase 3/7 activity suggested ISAE-induced apoptosis. Furthermore, ISAE alone could increase the phosphorylation of CDK1 at Y15 and activate the ATR/CHK1/Wee1/CDC25C signaling pathway. However, the addition of caffeine, a widely used ATR inhibitor to ISAE, reduced the phosphorylation of ATR, CHK1, and CDK1, as well as G2/M arrest in Jurkat cells. Moreover, increased phospho-H2A.X stained cells indicated the involvement of DNA damage in the anti-leukemic effect of ISAE. Finally, qualitative analysis using UPLC-tandem mass spectroscopy and molecular networking revealed that tryptanthrin was the most abundant organoheterocyclic metabolite in ISAE. At equivalent concentrations to ISAE, tryptanthrin induced G2/M arrest of Jurkat cells, which can be prevented by caffeine. CONCLUSIONS: ISAE causes G2/M arrest via activating ATR/CHK1/CDK1 pathway and tryptanthrin is one of the active components of ISAE. Our findings provide subtle support to the traditional use of I. suffruitcosa in leukemia management in folk medicine.

Conservation genetics and potential geographic distribution modeling of Corybas taliensis, a small 'sky Island' orchid species in China.

BACKGROUND: Corybas taliensis is an endemic species of sky islands in China. Its habitat is fragile and unstable, and it is likely that the species is threatened. However, it is difficult to determine the conservation priority or unit without knowing the genetic background and the overall distribution of this species. In this study, we used double digest restriction-site associated DNA-sequencing (ddRAD-seq) to investigate the conservation genomics of C. taliensis. At the same time, we modeled the extent of suitable habitat for C. taliensis in present and future (2030 and 2090) habitat using the maximum-entropy (MaxEnt) model. RESULTS: The results suggested that the related C. fanjingshanensis belongs to C. taliensis and should not be considered a separate species. All the sampling locations were divided into three genetic groups: the Sichuan & Guizhou population (SG population), the Hengduan Mountains population (HD population) and Himalayan population (HM population), and we found that there was complex gene flow between the sampling locations of HD population. MT was distinct genetically from the other sampling locations due to the unique environment in Motuo. The genetic diversity (π, He) of C. taliensis was relatively high, but its contemporary effective population size (Ne) was small. C. taliensis might be currently affected by inbreeding depression, although its large population density may be able to reduce the effect of this. The predicted areas of suitable habitat currently found in higher mountains will not change significantly in the future, and these suitable habitats are predicted to spread to other higher mountains under future climate change. However, suitable habitat in relatively low altitude areas may disappear in the future. This suggests that C. taliensis will be caught in a 'summit trap' in low altitude areas, however, in contrast, the high altitude of the Himalaya and the Hengduan Mountains are predicted to act as 'biological refuges' for C. taliensis in the future. CONCLUSIONS: These results not only provide a new understanding of the genetic background and potential resource distribution of C. taliensis, but also lay the foundation for its conservation and management.

Target-Guided Isolation and Purification of Antioxidants from Urtica laetevirens Maxim. by HSCCC Combined with Online DPPH-HPLC Analysis.

Urtica laetevirens Maxim. is used extensively in traditional Chinese medicine (TCM) for its potent antioxidative properties. In this study, three antioxidants were purified from U. laetevirens. using HSCCC guided by online DPPH-HPLC analysis. Firstly, the online DPPH-HPLC analysis was performed to profile out the antioxidant active molecules in U. laetevirens. The ultrasonic-assisted extraction conditions were optimized by response surface methodology and the results showed the targeted antioxidant active molecules could be well enriched under the optimized extraction conditions. Then, the antioxidant active molecules were separated by high-speed countercurrent chromatography ethyl acetate/n-butanol/water (2:3:5, v/v/v) as the solvent system. Finally, the three targets including 16.8 mg of Isovitexin, 9.8 mg of Isoorientin, and 26.7 mg of Apigenin-6,8-di-C-ß-d-glucopyranoside were obtained from 100 mg of sample. Their structures were identified by 1H NMR spectroscopy.

Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells.

The combination of compounds with complementary bioactivities into hybrid molecules is an emerging concept in drug discovery. In this study, we aimed to synthesize new hybrid compounds based on p53-MDM2/X protein-protein interaction spiropyrazoline oxindole-based inhibitors and ataxia telangiectasia and Rad3-related (ATR) protoflavone-based inhibitors through copper(i) catalysed azide-alkyne cycloaddition. Five new hybrids were prepared along with three representative reference fragments. The compounds were tested against human breast cancer cell lines MCF-7 (hormone-dependent, wild-type p53) and MDA-MB-231 (triple-negative, mutant p53). Most of the new hybrids were more cytotoxic than their reference fragments and several showed 2-4 times selective toxicity against MDA-MB-231 cells. Relevant pharmacological benefit gained from the hybrid coupling was further confirmed by virtual combination index calculations using the Chou method. Compound 13 modulated doxorubicin-induced DNA damage response through inhibiting the ATR-dependent activation of Chk-1, while increasing the activation of Chk-2. Our results suggest that the new hybrids may serve as new leads against triple negative breast cancer.

Ethylene controls cambium stem cell activity via promoting local auxin biosynthesis.

The vascular cambium is the main secondary meristem in plants that produces secondary phloem (outside) and xylem (inside) on opposing sides of the cambium. The phytohormone ethylene has been implicated in vascular cambium activity, but the regulatory network underlying ethylene-mediated cambial activity remains to be elucidated. Here, we found that PETAL MOVEMENT-RELATED PROTEIN1 (RhPMP1), an ethylene-inducible HOMEODOMAIN-LEUCINE ZIPPER I transcription factor in woody plant rose (Rosa hybrida), regulates local auxin biosynthesis and auxin transport to maintain cambial activity. Knockdown of RhPMP1 resulted in smaller midveins and reduced auxin content, while RhPMP1 overexpression resulted in larger midveins and increased auxin levels compared with the wild-type plants. Furthermore, we revealed that Indole-3-pyruvate monooxygenase YUCCA 10 (RhYUC10) and Auxin transporter-like protein 2 (RhAUX2), encoding an auxin biosynthetic enzyme and an auxin influx carrier, respectively, are direct downstream targets of RhPMP1. In summary, our results suggest that ethylene promotes an auxin maximum in the cambium adjacent to the xylem to maintain cambial activity.

Effects of cadmium stress on fruits germination and growth of two herbage species.

Cadmium (Cd) pollution is a global environmental problem. It is of great significance to find a kind of pasture that can grow normally in a cadmium environment, especially in the Tibetan Plateau. We studied the fruit germination and fruit growth of Elymus sinsubmuticus S.L. Chen and Elymus tangutorum (Nevski), native plants of the Tibetan Plateau, in different cadmium environments. The results showed that with increased cadmium stress, the fruit germination rate, final germination rate, fruit-vigor, average germination time, and germination-speed index for the two grass species gradually decreased, and the 50% germination time for the seed gradually increased. Root length, biomass, and the number of leaves decreased in both species. We quantified the fruit germination and growth of plants in the cadmium environment and found that E. sinosubmuticus S.L. Chen had better fruit germination and fruit growth, and it had the development potential of cadmium pollution control.

Effects of Cd treatment on morphology, chlorophyll content and antioxidant enzyme activity of Elymus nutans Griseb., a native plant in Qinghai-Tibet Plateau.

Cd pollution is a global environmental problem. However, the response mechanism of the alpine plant Pelagia under Cd stress remains unclear. Therefore, in this study, a native plant(Elymus nutans Griseb.) of the Qinghai-Tibet Plateau was used as the material to quantify plant height, leaf number, length of leaf, crown width, root number, biomass, Dry weight malondialdehyde (MDA), free proline, superoxide dismutase (SOD), ascorbate enzyme (APX), catalase (CAT) and chlorophyll contents under different Cd concentrations. The results showed that the growth of Elymus nutans Griseb. was a phenomenon of "low concentration promotes growth, high concentration inhibited growth" under Cd treatment. It meant that 10 mg·L-1 Cd promoted the growth of leaf number, plant height, crown width and tiller number, while 40 mg·L-1 Cd inhibited the growth of root number and biomass of Elymus nutans Griseb. compare with the control. The MDA content, free proline content, SOD activity, APX activity and CAT activity of Elymus nutans Griseb. was increased with the increase of Cd treatment concentration to resist the oxidative damage caused by Cd to the body. At the same time, the accumulation of chlorophyll A, chlorophyll B and chlorophyll AB was decreased with the increase of Cd stress concentration. In addition, the carotenoid content did not change much between the control group and the treatment group, indicating that Cd treatment had little effect on it. The results could provide a reference for the mechanism of heavy metal resistance and the selection and improvement of Cd -resistant varieties of Elymus nutans Griseb.

Loss of Rose Fragrance under Chilling Stress Is Associated with Changes in DNA Methylation and Volatile Biosynthesis.

Rose plants are widely cultivated as cut flowers worldwide and have economic value as sources of natural fragrance and flavoring. Rosa 'Crimson Glory', whose petals have a pleasant fragrance, is one of the most important cultivars of edible rose plants. Flower storage at low-temperature is widely applied in production to maintain quality; however, chilling results in a decrease in aromatic volatiles. To determine the molecular basis underlying the changes in aromatic volatile emissions, we investigated the changes in volatile compounds, DNA methylation patterns, and patterns of the transcriptome in response to chilling temperature. The results demonstrated that chilling roses substantially reduced aromatic volatile emissions. We found that these reductions were correlated with the changes in the methylation status of the promoters and genic regions of the genes involved in volatile biosynthesis. These changes mainly occurred for CHH (H = A, T, or C) which accounted for 51% of the total methylation. Furthermore, transcript levels of scent-related gene Germacrene D synthase (RhGDS), Nudix hydrolase 1 (RhNUDX1), and Phenylacetaldehyde reductase (RhPAR) of roses were strikingly depressed after 24 h at low-temperature and remained low-level after 24 h of recovery at 20 °C. Overall, our findings indicated that epigenetic regulation plays an important role in the chilling tolerance of roses and lays a foundation for practical significance in the production of edible roses.

New Verticillene Diterpenoids, Eudesmane Sesquiterpenoids, and Hydroperoxysteroids from the Further Chemical Investigation of a Taiwanese Soft Coral Cespitularia sp.

An investigation of the chemical composition of a Formosan soft coral Cespitularia sp. led to the discovery of one new verticillene-type diterpenoid, cespitulactam M (1); one new eudesmane sesquiterpenoid, cespilamide F (2); and three new hydroperoxysteroids (3-5) along with twelve known analogous metabolites (6-17). In addition, one new derivative, cespitulactam M-6,2'-diacetate (1a), was prepared from compound 1. The structures were determined by detailed spectroscopic analyses, particularly HRESIMS and NMR techniques. Moreover, the in vitro cytotoxicity, anti-inflammatory, and antibacterial activity of 1-17 and 1a were evaluated.

A draft Diabrotica virgifera virgifera genome: insights into control and host plant adaption by a major maize pest insect.

BACKGROUND: Adaptations by arthropod pests to host plant defenses of crops determine their impacts on agricultural production. The larval host range of western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is restricted to maize and a few grasses. Resistance of D. v. virgifera to crop rotation practices and multiple insecticides contributes to its status as the most damaging pest of cultivated maize in North America and Europe. The extent to which adaptations by this pest contributes to host plant specialization remains unknown. RESULTS: A 2.42 Gb draft D. v. virgifera genome, Dvir_v2.0, was assembled from short shotgun reads and scaffolded using long-insert mate-pair, transcriptome and linked read data. K-mer analysis predicted a repeat content of ≥ 61.5%. Ortholog assignments for Dvir_2.0 RefSeq models predict a greater number of species-specific gene duplications, including expansions in ATP binding cassette transporter and chemosensory gene families, than in other Coleoptera. A majority of annotated D. v. virgifera cytochrome P450s belong to CYP4, 6, and 9 clades. A total of 5,404 transcripts were differentially-expressed between D. v. virgifera larvae fed maize roots compared to alternative host (Miscanthus), a marginal host (Panicum virgatum), a poor host (Sorghum bicolor) and starvation treatments; Among differentially-expressed transcripts, 1,908 were shared across treatments and the least number were between Miscanthus compared to maize. Differentially-expressed transcripts were enriched for putative spliceosome, proteosome, and intracellular transport functions. General stress pathway functions were unique and enriched among up-regulated transcripts in marginal host, poor host, and starvation responses compared to responses on primary (maize) and alternate hosts. CONCLUSIONS: Manual annotation of D. v. virgifera Dvir_2.0 RefSeq models predicted expansion of paralogs with gene families putatively involved in insecticide resistance and chemosensory perception. Our study also suggests that adaptations of D. v. virgifera larvae to feeding on an alternate host plant invoke fewer transcriptional changes compared to marginal or poor hosts. The shared up-regulation of stress response pathways between marginal host and poor host, and starvation treatments may reflect nutrient deprivation. This study provides insight into transcriptomic responses of larval feeding on different host plants and resources for genomic research on this economically significant pest of maize.

Severinia buxifolia-isolated acridones inhibit lung cancer invasion and decrease HIFα protein synthesis involving 5'UTR-mediated translation inhibition.

BACKGROUND: Lung cancer is one of the most common cancers worldwide and is by far the leading cause of cancer death attributed to its rapid metastasis and poor prognosis. Given that hypoxia-inducible factors (HIFs) are associated with cancer metastasis, discovering agents to inhibit HIF-mediated invasive cancer is highly desired. PURPOSE: This study aimed to investigate the natural acridone compounds isolated from Severinia buxifolia for the potential to delay hypoxia-induced lung cancer invasiveness by HIF inhibition. METHODS: Using a hypoxia-responsive element (HRE) luciferase reporter, cell migration and invasion assays, real-time PCR, Western blot, and DNA recombinant clones, compound effect on HIF activity, cancer metastasis, HIF-1α mRNA transcription, HIFs protein stability, and HIF-1α translation were observed under hypoxia conditions. RESULTS: Atalaphyllidine (Sbs-A) and atalaphyllinine (Sbs-B) were found to show the most potent effects on HIF transcriptional activity and HIF-1α protein expression in NSCLC cell line A549, although Sbs-A and Sbs-B might not attribute decreasing HIF-1α mRNA expression to potent inhibition of HIF activity. HIF-1α protein stability was not affected by Sbs-A; also, prolyl hydroxylase and proteasome inhibitors could not reverse the inhibitory effect from compounds. Furthermore, 3 - 10 µM low concentrations of Sbs-A inhibited HIF target gene expression, gelatin zymography activity, and A549 cancer invasion. Ultimately, Sbs-A inhibited HIF-1α 5'UTR-mediated translation independent of oxygen concentration, underlying the mechanism of compounds inhibiting HIF-1α protein expression. CONCLUSION: Our study proposed Severinia buxifolia-isolated acridone compounds inhibited 5'-mRNA HIFA-mediated translation and provided evidence supporting the ability of acridone compounds in targeting HIFα for delayed lung cancer metastasis.

Ecological Niche and Interspecific Association of Plant Communities in Alpine Desertification Grasslands: A Case Study of Qinghai Lake Basin.

The study of niche and interspecific relationships is one of the classical ecological theories. We set up four desertification gradients. The "Levins" and "Pianka" method were used to calculate the species' niche breadth and niche overlap. Interspecies associations were analyzed by the ratio of variance (VR), Chi-square test, association coefficient (AC) and Ochiai index (OI). The results showed that in grasslands with different degrees of desertification, Stellera chromosome (3.90), Thermopsis lanceolate (3.52) and Aster almanacs (3.99) had larger niche widths, which were wide-area species of plant communities in the desertification area. The ecological niches of the same species in different habitats or different species in the same habitat were multi-dimensional. Niche differentiation measured by niche overlap can occur at any community succession stage. Niche width and niche overlap were not always consistent with environmental changes. Moreover, there was no linear relationship between them. The interspecific connection coefficient fluctuated greatly with the environment. The results can provide a reference for the study of plant community competition mechanism and desertification control in desertification land of the study area. We still do not know the mechanism of how the plants were preserved and how the retained plants adapted to the new environment during the desertification process. We can further study these questions in the next step.

Ethiodized poppyseed oil-based contrast medium is superior to water-based contrast medium during hysterosalpingography regarding image quality improvement and fertility enhancement: A multicentric, randomized and controlled trial.

Background: The efficacy of ethiodized poppyseed oil in hysterosalpingography (HSG) image quality and fertility enhancement has been revealed, but whether this HSG modality has similar effects in the Chinese population is still unclear. Methods: Between July 18, 2017, and December 29, 2019, this multicentric, randomized, two-arm, clinical trial was performed involving 15 medical centers. Infertile women meeting HSG indications were randomly assigned to an oil group and a water group. The coprimary outcome included HSG image quality during HSG and fertility-enhancing effects of HSG. This study was registered on ClinicalTrials.gov (NCT03370575). Findings: A total of 1026 subjects were randomly assigned to an oil group (N = 508) and a water group (N = 518). HSG image quality revealed that the oil group had outstanding visualization (all P < 0.001); total image quality scores for uterus opacification or uterine outline (2.9 ± 0.4 vs. 2.7 ± 0.5), fallopian tube outline (2.3 ± 0.8 vs. 1.7 ± 0.7), fimbrial rugae (1.7 ± 1.0 vs. 1.3 ± 0.8), fallopian tube spillage (2.1 ± 0.9 vs. 1.6 ± 0.8), peritoneal distribution (2.6 ± 0.9 vs. 2.1 ± 1.0) and diagnostic quality (11.6 ± 3.4 vs. 9.5 ± 3.1) (all P < 0.001) were higher in the oil group than in the water group. Regarding fertility-enhancing evaluation, the oil group showed an increased cumulative on-going pregnancy rate, on-going pregnancy within 6 months (29.1% vs. 20.1%), clinical pregnancy (39.5% vs. 29.1%) and live birth ≥ 24 weeks of gestation (36.1% vs. 27.7%) but a shorter time to pregnancy than the water group (all P < 0.01). Concerning adverse events, the oil group showed a lower occurrence rate of abdominal pain and vaginal bleeding after HSG (both P < 0.01). Interpretation: Ethiodized poppyseed oil-based contrast is superior to water-based contrast during HSG in terms of image quality improvement and fertility enhancement. This study indicates the priority of the application of ethiodized poppyseed oil-based contrast during the HSG procedure in infertile patients. Funding: No funding was received.

3,5,2',4'-Tetramethoxystilbene, a fully methylated resveratrol analog, prevents platelet aggregation and thrombus formation by targeting the protease-activated receptor 4 pathway.

Thrombin is a potent platelet activator and a key mediator of blood coagulation, thereby playing a crucial role in cardiovascular disease. Recently, protease-activated receptor 4 (PAR4), one of thrombin receptors in human platelets, is emerging as a promising target for antiplatelet therapy. 3,5,2',4'-Tetramethoxystilbene (TMS), a resveratrol analog, have demonstrated promising effects on preventing atherosclerosis and hypertension, whereas its antiplatelet effect has never been investigated. Herein we show that TMS at concentrations of a few micromolar selectively inhibits PAR4-mediated human platelet aggregation, ATP secretion, integrin αIIbß3 activation, and signaling pathways. In a whole-blood model of arterial flow, TMS also significantly reduced in vitro thrombus formation. Analysis of the structure-activity relationships of TMS and a panel of stilbene analogs reveal that full methylation of hydroxy groups of the stilbenes is the critical structural determinant for the anti-PAR4 activity. Our results suggest that fully methylated resveratrol analogs with anti-PAR4 activity are potential candidates for development of novel antiplatelet agents.

A Randomized Cohort Study: Is It Worth the Time to Receive Antiandrogenic Pretreatment Before Ovulation Induction for Women With Polycystic Ovary Syndrome?

Objective: To assess the effect of antiandrogenic pretreatment using combined oral contraceptives (COCs) before ovulation induction in infertile patients with polycystic ovary syndrome (PCOS) with hyperandrogenism. Design: Prospective, randomized open-labeled cohort study. Setting: Multicenter. Patients: PCOS patients with hyperandrogenism and requiring infertility treatments. Interventions: Randomization to direct ovulation induction of letrozole (letrozole group) or ethinylestradiol/cyproterone acetate (EE/CPA) for 3 months and subsequent letrozole-induced ovulation (EE/CPA+ letrozole group). The maximum number of ovulation induction cycle was three to four. Main Outcome Measures: Ovulation rate, conception rate, ongoing pregnancy rate, and live birth rate were the main outcomes of the study. Results: There were no significant differences in the cumulative ovulation, conception, ongoing pregnancy, and live birth rates between the letrozole and EE/CPA+ letrozole groups (cumulative ovulation: 206/254 [81.10%] vs. 169/205 [82.44%], risk ratio [RR]= 1.09 [0.68,1.76], P=0.713; conception: 44/90 [48.89%] vs. 42/76 [55.26%], RR= 1.29 [0.70,2.38], P=0.413; ongoing pregnancy: 33/90 [36.67%] vs. 33/76 [43.42%], RR=1.33 [0.71,2.47], P=0.376; and live birth: 32/90 [35.56%] vs. 31/76 [40.79%], RR=1.25 [0.67, 2.34], P=0.489). Conclusions: The results of this study showed that COC pretreatment was not superior to direct letrozole-induced ovulation therapy in improving ovulation and pregnancy results in women with PCOS. There is no benefit to perform antiandrogenic therapy before ovulation induction in patients with PCOS in clinical practice. Clinical Trial Registration: www.clinicaltrials.gov, identifier ChiCTR1900022839.