Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells.

BACKGROUND: Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. METHODS: The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA+ B cells. RESULTS: HCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8+ T lymphocyte activation was enhanced in the absence of IL-21R due to the reduction of immunosuppressive IgA+ B cells. Mechanistically, the IL-21R-STAT1-c-Jun/c-Fos regulatory axis was activated in MASH-driven HCC and thus promoted the transcription of Igha, resulting in the induction of IgA+ B cells. CONCLUSIONS: IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy.

Transmission dynamics of a reaction-advection-diffusion dengue fever model with seasonal developmental durations and intrinsic incubation periods.

In this paper, we propose a reaction-advection-diffusion dengue fever model with seasonal developmental durations and intrinsic incubation periods. Firstly, we establish the well-posedness of the model. Secondly, we define the basic reproduction number ℜ 0 for this model and show that ℜ 0 is a threshold parameter: if ℜ 0 < 1 , then the disease-free periodic solution is globally attractive; if ℜ 0 > 1 , the system is uniformly persistent. Thirdly, we study the global attractivity of the positive steady state when the spatial environment is homogeneous and the advection of mosquitoes is ignored. As an example, we use the model to investigate the dengue fever transmission case in Guangdong Province, China, and explore the impact of model parameters on ℜ 0 . Our findings indicate that ignoring seasonality may underestimate ℜ 0 . Additionally, the spatial heterogeneity of transmission may increase the risk of disease transmission, while the increase of seasonal developmental durations, intrinsic incubation periods and advection rates can all reduce the risk of disease transmission.

Genome-wide association study and genomic prediction for resistance to brown planthopper in rice.

The brown planthopper (BPH) is the most destructive insect pest that threatens rice production globally. Developing rice varieties incorporating BPH-resistant genes has proven to be an effective control measure against BPH. In this study, we assessed the resistance of a core collection consisting of 502 rice germplasms by evaluating resistance scores, weight gain rates and honeydew excretions. A total of 117 rice varieties (23.31%) exhibited resistance to BPH. Genome-wide association studies (GWAS) were performed on both the entire panel of 502 rice varieties and its subspecies, and 6 loci were significantly associated with resistance scores (P value < 1.0e-8). Within these loci, we identified eight candidate genes encoding receptor-like protein kinase (RLK), nucleotide-binding and leucine-rich repeat (NB-LRR), or LRR proteins. Two loci had not been detected in previous study and were entirely novel. Furthermore, we evaluated the predictive ability of genomic selection for resistance to BPH. The results revealed that the highest prediction accuracy for BPH resistance reached 0.633. As expected, the prediction accuracy increased progressively with an increasing number of SNPs, and a total of 6.7K SNPs displayed comparable accuracy to 268K SNPs. Among various statistical models tested, the random forest model exhibited superior predictive accuracy. Moreover, increasing the size of training population improved prediction accuracy; however, there was no significant difference in prediction accuracy between a training population size of 737 and 1179. Additionally, when there existed close genetic relatedness between the training and validation populations, higher prediction accuracies were observed compared to scenarios when they were genetically distant. These findings provide valuable resistance candidate genes and germplasm resources and are crucial for the application of genomic selection for breeding durable BPH-resistant rice varieties.

Multi-stable and spatiotemporal staggered patterns in a predator-prey model with predator-taxis and delay.

The effects of predator-taxis and conversion time delay on formations of spatiotemporal patterns in a predator-prey model are explored. First, the well-posedness, which implies global existence of classical solutions, is proved. Then, we establish critical conditions for the destabilization of the coexistence equilibrium via Turing/Turing-Turing bifurcations by describing the first Turing bifurcation curve; we also theoretically predict possible bistable/multi-stable spatially heterogeneous patterns. Next, we demonstrate that the coexistence equilibrium can also be destabilized via Hopf, Hopf-Hopf and Turing-Hopf bifurcations; also possible stable/bistable spatially inhomogeneous staggered periodic patterns and bistable spatially inhomogeneous synchronous periodic patterns are theoretically predicted. Finally, numerical experiments also support theoretical predictions and partially extend them. In a word, theoretical analyses indicate that, on the one hand, strong predator-taxis can eliminate spatial patterns caused by self-diffusion; on the other hand, the joint effects of predator-taxis and conversion time delay can induce complex survival patterns, e.g., bistable spatially heterogeneous staggered/synchronous periodic patterns, thus diversifying populations' survival patterns.

Exosomal circRNA RHOT1 promotes breast cancer progression by targeting miR-204-5p/ PRMT5 axis.

BACKGROUND: Circular RNA RHOT1 (circRHOT1) plays crucial roles in tumorigenesis by competing with microRNAs. It is largely abundant in tumor cell-derived exosomes. Meanwhile, cancer-derived exosomes participate in diverse biological processes. However, the expression patterns and functions of exosomal circRHOT1 in breast cancer remain unknown. This study is aimed to investigate and elucidate the exosomal circRHOT1/miR-204-5p/PRMT5 axis in breast cancer. METHODS: The exosomes derived from serum samples of breast cancer patients and breast cancer cell lines were characterized using transmission electron microscopy and Western blot. MTT, colony formation, wound healing, and transwell assays were utilized to analyze cell proliferation, migration, and invasion of breast cancer cells. Flow cytometry was used for apoptosis analysis. The bioinformatics method was employed to screen differentially expressed novel circRNAs and predict the microRNA targets of circRHOT1. Dual-luciferase reporter gene assays were performed to verify their direct interaction. Finally, Xenograft experiments were used to investigate the effect of exosomal circRHOT1 on tumor growth in vivo. RESULTS: CircRHOT1 exhibited significantly high expression in exosomes derived from the serum of breast cancer patients and breast cancer cell lines, which suggested its potential diagnostic value. Breast cancer-derived exosomes promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells while inhibiting apoptosis. However, exosomes with downregulated circRHOT1 inhibited the growth of co-cultured cells. Mechanistically, circRHOT1 acted as a sponge of miR-204-5p and promoted protein arginine methyltransferase 5 (PRMT5) expression. Moreover, miR-204-5p inhibitor and pcPRMT5 could reverse the tumor suppressive effects mediated by circRHOT1-knockdown. Furthermore, treatment with exosomes derived from breast cancer cells with circRHOT1 knockdown attenuated tumor growth in tumor-bearing nude mice, which was accompanied by a reduction in PRMT5 expression and an enhancement of miR-204-5p expression. CONCLUSION: The exosomal circRHOT1 may promote breast cancer progression by regulating the miR-204-5p/PRMT5 axis. The current study strengthens the role of circRHOT1, miR-204-5p, and PRMT5 in breast cancer development and provides a potential treatment strategy for breast cancer.

Effect of short-term compression therapy after thermal ablation for varicose veins: study protocol for a prospective, multicenter, non-inferiority, randomized controlled trial.

BACKGROUND: For patients with varicose veins, the goal is to relieve pain and swelling, reduce the severity of edema, improve skin changes, and heal ulcers associated with venous disease. Compression therapy is the cornerstone of their management. Several studies have shown that wearing an elastic bandage for the first 24 h and then a compression stocking for a week can effectively reduce the pain after thermal ablation. However, in clinical practice, patient compliance with this treatment could be better, considering difficulties in pulling up and removing the compression stocking, tightness, and skin irritation because these must be worn for a prolonged period. A potential solution to battling these barriers is short-term compression therapy. Besides, the effect and necessity of wearing compression stockings after thermal ablation have been questioned. Based on current clinical experience and limited evidence, although some scholars have suggested that compression therapy may be an unnecessary adjunctive therapy after thermal ablation, there is still a great deal of uncertainty in the absence of compression therapy after thermal ablation compared to compression therapy. Therefore, we advocate further research to evaluate the clinical effect of short-term postoperative compression therapy. Furthermore, well-designed randomized controlled trials are needed. METHODS: A prospective, multicenter, non-inferiority randomized controlled trial is designed to evaluate the non-inferiority of target vein occlusion rate at 3 months. Three hundred and sixty patients will be randomly assigned in a 1:1 ratio to one of the following treatments: (A) 3 M™ Coban™ elastic bandage for 48 h or (B) 3 M™ Coban™ elastic bandage for the first 24 h and then a class II compression full-length stocking (23-32 mm Hg) for 1 week. The two groups will be compared on several variables, including target vein occlusion rate at 3 months (primary outcome indicator), pain, quality of life, clinical severity of varicose veins, postoperative complications, time to return to regular work, and compliance. DISCUSSION: Suppose the effect of the 3 M™ Coban™ elastic bandage for 48 h proves to be non-inferior to long-term compression therapy. In that case, this short-term treatment may contribute to a future update of clinical guidelines for compression therapy after thermal ablation of varicose veins, resulting in higher patient compliance and better postoperative quality of life. TRIAL REGISTRATION: Clinical Trials NCT05840991 . Registered on May 2023.

The interaction of nicotinic acetylcholine receptor subunits Ldα3, Ldα8 and Ldß1 with neonicotinoids in Colorado potato beetle, Leptinotarsa decemlineata.

The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is an extremely destructive notifiable quarantine pest. Over the last two decades, neonicotinoid insecticides, particularly thiamethoxam and imidacloprid, have been used to control it in Xinjiang, and local field populations have developed different levels of resistance in consequence. However, the contributions of nicotinic acetylcholine receptors (nAChRs) to neonicotinoid resistance are currently poorly understood in CPB. Previous studies have shown that nAChRα1, α3, α8 and ß1 are major target subunits for neonicotinoids in some model and important agricultural insects including nAChRα1 subunit of L. decemlineata (Ldα1). In this study, the expression levels of Ldα3, Ldα8 and Ldß1 following 72 h of treatments with median lethal doses of thiamethoxam and imidacloprid were compared using real-time quantitative PCR. These genes were then individually and simultaneously knocked down with Ldα1 by RNA interference (RNAi) using a double-stranded RNA (dsRNA) feeding method for six days to explore their roles in CPB susceptibility to imidacloprid and thiamethoxam. The results showed that the expressions of Ldα3, Ldα8 and Ldß1 were significantly decreased by 36.99-74.89% after thiamethoxam and imidacloprid treatments, compared with the control. The significant downregulation of the target genes resulting from RNAi significantly reduced the mortality of adults exposed to thiamethoxam and imidacloprid by 34.53% -56.44% and 28.78%-43.93%, respectively. Furthermore, the adult survival rates were not affected by every dsRNA-feeding treatment, while the body weight of the test adults significantly deceased after four and six days of individual gene RNAi. This study showed that Ldα3, Ldα8 and Ldß1 are down-regulated by thiamethoxam and imidacloprid and play important roles in the tolerance of CPB to neonicotinoids.

Large scale rice germplasm screening for identification of novel brown planthopper resistance sources.

Rice (Oryza sativa L.) is a staple food crop globally. Brown planthopper (Nilaparvata lugens Stål, BPH) is the most destructive insect that threatens rice production annually. More than 40 BPH resistance genes have been identified so far, which provide valuable gene resources for marker-assisted breeding against BPH. However, it is still urgent to evaluate rice germplasms and to explore more new wide-spectrum BPH resistance genes to combat newly occurring virulent BPH populations. To this end, 560 germplasm accessions were collected from the International Rice Research Institute (IRRI), and their resistance to current BPH population of China was examined. A total of 105 highly resistant materials were identified. Molecular screening of BPH resistance genes in these rice germplasms was conducted by developing specific functional molecular markers of eight cloned resistance genes. Twenty-three resistant germplasms were found to contain none of the 8 cloned BPH resistance genes. These accessions also exhibited a variety of resistance mechanisms as indicated by an improved insect weight gain (WG) method, suggesting the existence of new resistance genes. One new BPH resistance gene, Bph44(t), was identified in rice accession IRGC 15344 and preliminarily mapped to a 0-2 Mb region on chromosome 4. This study systematically sorted out the corresponding relationships between BPH resistance genes and germplasm resources using a functional molecular marker system. Newly explored resistant germplasms will provide valualble donors for the identification of new resistance genes and BPH resistance breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01416-x.

Efficacy and Safety of Gabapentin in Improving Sleep Quality of Patients with Sensory Nervous System Diseases: A Meta-Analysis.

Context: Sensory nervous-system diseases are chronic diseases that injury or disease of the somatosensory nervous system causes. Sleep disorders usually accompany these diseases, and in turn, worsen their conditions and form a vicious circle that brings great difficulties in clinical treatment. Objective: The study intended to systematically evaluate the clinical efficacy and safety of gabapentin in improving the sleep quality of patients with sensory nervous-system diseases using a meta-analysis, so as to provide evidence-based medical evidence for clinical treatment. Design: The research team performed a comprehensive narrative review by searching the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), WANFANG, Chinese Biomedical Database (CBM), PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases. The search terms included gabapentin, 1-(aminomethyl)-cyclohexaneacetic acid, gabapentin hexal, gabapentin-ratiopharm, sleep, and insomnia. Setting: The review took place in the Department of Neurology at the First People's Hospital of Linping District in Hangzhou, China. Outcome Measures: The research team extracted the data from the studies meeting the inclusion criteria and then transferred them into the Review Manager 5.3 software for meta-analysis. The outcome measures included scores: (1) for the improvement in the degree of sleep interference score; (2) for the improvement in sleep quality; (3) for the rate of poor sleep quality; (4) for the rate awakenings of >5 per night; and (5) for the incidence of adverse reactions. Results: The research team found eight RCTs with 1269 participants, including 637 participants in a gabapentin test group and 632 participants in the placebo control group. The meta-analysis showed that the decrease in the degree of sleep interference [mean deviation (MD) = -0.86, 95% CI: (-0.91, -0.82), P < .00001] and the improvement in sleep quality [odds ratio (OR) = 2.64, 95% CI: (1.90, 3.67), P < .00001] in gabapentin group were significantly higher than those in placebo group (P < .05), while the rate of poor sleep quality [OR = 0.43, 95% CI: (0.23, 0.79), P = .007] and the rate of > 5 night awakenings [OR = 0.01, 95% CI: (0.05, 0.70), P = .01] in gabapentin group were significantly lower than those in placebo group (P < .05). No statistically significant differences existed in the incidence of adverse reactions between the two groups. Conclusions: Gabapentin is safe and effective in improving the sleep quality of patients with sensory nervous-system diseases. Due to the limitations of sample size and types of diseases in the current study, the field needs multicenter, large-sample, and high-quality RCTs for further validation in the future.

Celastrol Supplementation Ablates Sexual Dimorphism of Abdominal Aortic Aneurysm Formation in Mice.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are permanent dilations of the abdominal aorta with 4-5 times greater prevalence in males than in females. The aim of this study is to define whether Celastrol, a pentacyclic triterpene from the root extracts of Tripterygium wilfordii, supplementation influences angiotensin II (AngII)-induced AAAs in hypercholesterolemic mice. METHODS: Age-matched (8-12 weeks old) male and female low-density lipoprotein (Ldl) receptor-deficient mice were fed a fat-enriched diet supplemented with or without Celastrol (10 mg/kg/day) for five weeks. After one week of diet feeding, mice were infused with either saline (n = 5 per group) or AngII (500 or 1000 ng/kg/min, n = 12-15 per group) for 28 days. RESULTS: Dietary supplementation of Celastrol profoundly increased AngII-induced abdominal aortic luminal dilation and external aortic width in male mice as measured by ultrasonography and ex vivo measurement, with a significant increase in incidence compared to the control group. Celastrol supplementation in female mice resulted in significantly increased AngII-induced AAA formation and incidence. In addition, Celastrol supplementation significantly increased AngII-induced aortic medial elastin degradation accompanied by significant aortic MMP9 activation in both male and female mice compared to saline and AngII controls. CONCLUSIONS: Celastrol supplementation to Ldl receptor-deficient mice ablates sexual dimorphism and promotes AngII-induced AAA formation, which is associated with increased MMP9 activation and aortic medial destruction.

Versatile halogenation via a CNHC

Stable cyclopalladated complexes containing an (sp3)C-Pd bond were synthesized via α-CH2 deprotonation and palladation of N-alkyl groups of carbene ligands bearing electron-withdrawing substituents. The strong electron donating strengths of the resulting CNHC^Csp3 chelators were experimentally identified, and the palladacycle underwent template-directed, versatile C-halogenation with X2.

Copper-Catalyzed Annulation of O-Acyl Oximes with Cyclic 1,3-Diones for the Synthesis of 7,8-Dihydroindolizin-5(6H)-ones and Cyclohexanone-Fused Furans.

A copper-catalyzed annulation of O-acyl oximes with cyclic 1,3-diones has been developed for the concise synthesis of 7,8-dihydroindolizin-5(6H)-ones and cyclohexanone-fused furans through the substituent-controlled selective radical coupling process. 2-Alkyl cyclic 1,3-diones undergo C-C radical coupling, while 2-unsubstituted cyclic 1,3-diones undergo C-O radical coupling.

Elevated serum progesterone levels on the hCG trigger day have a negative impact on the live birth rate in the first fresh IVF-ET cycle.

To investigate whether there is a relationship between elevated serum progesterone (PROG) on the hCG trigger day and the live birth rate (LBR) in IVF/ICSI cycles, the retrospective analysis was carried out from the patients undergoing the first ART cycles throughout 2016. The PROG levels were measured on the hCG trigger day. The LBR, clinical pregnancy rate (CPR), implantation rate (IR) and other parameter rate values were compared among the three different PROG elevations. A total of 2550 IVF/ICSI cycles fulfilling all the inclusion and exclusion criteria were selected. Finally, three groups [PROG <0.40 ng/mL, 0.40 ≤ PROG < 1.5 ng/mL, PROG ≥ 1.5 ng/mL] were categorised based on the serum PROG levels. LBR, CPR and IR declined as the PROG value increased, while there was no difference in the embryo utilisation rates. Serum PROG levels on the day of hCG administration were negatively associated with the LBR, even in ETs with a good prognosis.Impact StatementWhat is already known on this subject? The clinical effects of PROG are still controversial. Some studies have confirmed that there was not too much association between premature elevation of PROG and live birth, some are still convincing that there is a negative correlation and will result in ART cycles of pregnancy and LBR reduction.What do the results of this study add? Our data substantiated that the high serum PROG level had the lowest LBR, IR and CPR, but the embryo utilisation rate may not have too much to do with the elevated PROG.What are the implications of these findings for clinical practice and/or further research? This study further strengthens the negative impact of elevated PROG levels on pregnancy outcomes, and suggests that frozen thawed embryo transfer appears to be a reasonable and advantageous approach for this subset of patients.

CHD6 promotes broad nucleosome eviction for transcriptional activation in prostate cancer cells.

Despite being a member of the chromodomain helicase DNA-binding protein family, little is known about the exact role of CHD6 in chromatin remodeling or cancer disease. Here we show that CHD6 binds to chromatin to promote broad nucleosome eviction for transcriptional activation of many cancer pathways. By integrating multiple patient cohorts for bioinformatics analysis of over a thousand prostate cancer datasets, we found CHD6 expression elevated in prostate cancer and associated with poor prognosis. Further comprehensive experiments demonstrated that CHD6 regulates oncogenicity of prostate cancer cells and tumor development in a murine xenograft model. ChIP-Seq for CHD6, along with MNase-Seq and RNA-Seq, revealed that CHD6 binds on chromatin to evict nucleosomes from promoters and gene bodies for transcriptional activation of oncogenic pathways. These results demonstrated a key function of CHD6 in evicting nucleosomes from chromatin for transcriptional activation of prostate cancer pathways.

[Risk Factor Analysis of Abdominal Aortic Enlargement after Thoracic Endovascular Aortic Repair Using Two-Stent Graft Implantation for Stanford Type B Aortic Dissection].

Objective: To explore the risk factors of abdominal aortic enlargement (AAE) after thoracic endovascular aortic repair using two-stent graft implantation (TEVAR-TSI) for Stanford type B aortic dissection. Methods: The clinical and imaging data of patients who underwent TEVAR-TSI for Stanford type B aortic dissection in the First Affiliated Hospital of Hebei North University from January 2013 through September 2020 were retrospectively collected and analyzed. CT angiography (CTA) scans were performed before the procedure. Follow-up CTA scans were scheduled and performed in 1, 3, 6, and 12 months after the procedure and annually thereafter. The primary outcome was AAE. The risk factors of AAE after TEVAR-TSI were selected and survival analysis and multivariate logistic regression were conducted accordingly. Results: A total of 146 patients were regularly followed up at our hospital, with the median followup time of the entire cohort being 48 months (ranging from 12 to 84 months). During the followup period after TEVAR-TSI, the incidence of AAE was 19.9% (29/146). A total of 29 patients developed AAE (the AAE group), while 117 patients did not develop AAE (the non-AAE group). There were a total of 27 deaths, including 13 in the non-AAE group versus 14 in the AAE group. Distal aortic reoperation was performed on 10 patients, including 4 in the non-AAE group versus 6 in the AAE group. The cumulative long-term survival and freedom from distal aortic reoperation of the non-AAE group were both significantly better those of the AAE group ( P<0.05). Logistic multivariate regression analysis showed that independent risk factors of AAE after TEVAR-TSI included the following, partial thrombosis of the false lumen (odds ratio [ OR]=4.090, 95% confidence interval [ CI]: 1.539-10.867, P=0.005), the longer cumulative diameter of residual intimal tear above the level of the lowest renal arteries ( OR=1.290, 95% CI: 1.164-1.429, P=0.000), and shorter cumulative diameter of residual intimal tear below the level of the lowest renal arteries ( OR=0.487, 95% CI: 0.270-0.878, P=0.017). Conclusion: The prognosis of patients who developed AAE after TEVAR-TSI was not good. During followup visits, as precautions against the development of AAE, close attention should be paid to partial thrombosis of the false lumen, cumulative diameter of residual intimal tear above the level of the lowest renal arteries, and cumulative diameter of residual intimal tear below the level of the lowest renal arteries.

Development and Validation of Ferroptosis- and Immune-Related lncRNAs Signatures for Breast Infiltrating Duct and Lobular Carcinoma.

Background: Heterogeneity of breast cancer (BRCA) is significantly correlated with its prognosis. Target therapy for ferroptosis and immunity is a new cancer treatment option discovered in recent years. In the present study, we aimed to identify ferroptosis- and immune-related long non-coding RNAs (lncRNAs) to accurately predict the prognosis and diagnosis of patients with breast infiltrating duct and lobular carcinoma by integrated analyses. Methods: The corresponding data for the patients with breast infiltrating duct and lobular carcinoma by integrated analyses were obtained from The Cancer Genome Atlas (TCGA). Analyses of univariate and multivariate Cox regressions were used to identify the suitable candidate biomarkers. Results: We found that seven ferroptosis- and immune-related differentially expressed lncRNAs (FI-DELs) (AC007686.3, AC078883.1, ADAMTS9-AS1, AL035661.1, CBR3-AS1, FTX, and TMEM105) were correlated with the overall survival of patients with breast infiltrating duct and lobular carcinoma. The areas under the receiver operating characteristic (AUCs) value of the prognosis model were all over 0.6 in training, validation, and entire groups. The sensitivity and specificity of the diagnosis model was 87.84% and 97.06%, respectively. Conclusions: Through a series of bioinformatics analyses, we found that the seven FI-DELs could serve as prognostic and diagnostic biomarkers for patients with breast infiltrating duct and lobular carcinoma. However, whether these seven biomarkers could be really applied to the clinic requires further investigations.

The actions of neonicotinoid insecticides on nicotinic acetylcholine subunits Ldα1 and Ldα8 of Leptinotarsa decemlineata and assembled receptors.

The insect nicotinic acetylcholine receptor (nAChR) is a pentameric channel protein and also a target for neonicotinoids. There are few reported studies on the molecular interactions of Leptinotarsa decemlineata nAChRs with neonicotinoids. In this study, we analyzed the response of acetylcholine and neonicotinoids (thiamethoxam [TMX], imidacloprid [IMI], and clothianidin [CLO]) on hybrid receptors constructed by nAChR α1 and α8 subunits of L. decemlineata (Ldα1 and Ldα8) co-expressed with rat ß2 subunit (rß2) at different capped RNA (cRNA) ratios in Xenopus oocytes. In addition, we evaluated the expression changes of Ldα1 and Ldα8 after median lethal dose of TMX treatment for 72 h by quantitative polymerase chain reaction (qPCR). The resulting functional nAChRs Ldα1/rß2 and Ldα1/Ldα8/rß2 showed different pharmacological characteristics. The neonicotinoids tested showed lower agonist affinity on Ldα1/Ldα8/rß2 compared to Ldα1/rß2 at same ratios of subunit cRNAs. The sensitivities of neonicotinoids tested for Ldα1/rß2 and Ldα1/Ldα8/rß2 at cRNA ratios of 5:1, 1:1 and 5:5:1, 1:1:1, respectively, were lower than those for nAChRs at ratios of 1:5 and 1:1:5, respectively, whereas the values of maximum response (Imax ) varied. For Ldα1/Ldα8/rß2, a reduction of Lda8 cRNA resulted in increased sensitivity to IMI and decreased sensitivity to TMX. The expression of Ldα1 and Ldα8 significantly decreased in adults by 82.12% and 47.02%, respectively, while Ldα8 was significantly upregulated by 2.44 times in 4th instar larvae after exposure to TMX. We infer that Ldα1 and Ldα8 together play an important role in the sensitivity of L. decemlineata to neonicotinoids.

Blastocyst development rate influences singleton gestational age of similarly graded blastocysts after vitrified-warmed single embryo transfer cycles.

RESEARCH QUESTION: Does the development rate of blastocysts influence neonatal outcomes after blastocyst transfer cycles when the morphological score of the transferred blastocysts is similar? DESIGN: A retrospective study involving singleton live births born to 1280 women undergoing single frozen blastocyst transfers (FBTs) between January 2016 and December 2018 at a tertiary care centre. Patients were grouped into day-5 or day-6 groups depending on the development rate of blastocysts. These were further grouped into four groups based on the blastocyst inner cell mass and trophectoderm scoring: excellent (AA); good (AB or BA); average (AC, CA or BB); and poor (BC or CB). The primary outcomes were gestational age and singleton birth weight. RESULTS: Singletons resulting from day-5 single FBT were at a lower risk of preterm birth than those resulting from day-6 single FBT (adjusted OR 0.63, 95% CI 0.41 to 0.97, P = 0.035). In the day-5 good-quality blastocyst group and day-5 average-quality blastocyst group, singletons were at a lower risk of preterm birth than those resulting from day-6 groups, respectively (adjusted OR 0.22, 95% CI 0.08 to 0.63, P = 0.005 and adjusted OR 0.52, 95% CI 0.29 to 0.94, P = 0.03). CONCLUSIONS: Day-6 single FBT was associated with a higher risk of preterm birth compared with day-5 single FBT in good and average morphological scoring blastocysts. Our analysis was restricted to women with singleton births from single FBTs. Future prospective studies are required to confirm the findings.

Feedback control of pulsed-power generator based on solid-state linear transformer driver.

A pulsed-power generator based on the circuit scheme of a linear transformer driver (LTD) while using solid-state switches is referred to as a solid-state LTD (SSLTD). One of the advantages of the SSLTD compared with traditional pulsed-power generators is its flexibility in the output waveform. It has potential applications to atmospheric pressure gas discharge because this kind of discharge load usually exhibits a fast-changing impedance. In this paper, a feedback control system for SSLTDs is reported. It uses a system-on-chip analog-to-digital converter combined with a field programmable gate array. By using this system, our SSLTD has the ability to automatically adjust its output waveform based on the information obtained from the previous pulse. As a result, during repetitive operation, our SSLTD can figure out the right output waveform according to a user scenario and can respond to any variation that may occur on the load.

MicroRNA expression profiling involved in doxorubicin-induced cardiotoxicity using high-throughput deep-sequencing analysis.

MicroRNAs (miRNAs/miRs) are sensitive biomarkers and endogenous repressors of gene expression by decreasing mRNA stability and interfering with mRNA translation. Despite a number of investigations revealing the dysregulation of miRNA expression associated with cardiotoxicity induced by doxorubicin (Dox), perturbation of miRNAs directly resulting from Dox at early stage in cardiomyocytes and the target gene interaction remain largely unknown. In the present study, high-throughput deep-sequencing was used to analyze changes in global miRNA expression in H9c2 cardiomyocytes exposed to 5 µg/ml Dox for 0, 12 or 24 h. Compared with the 0-h time point, the expression levels of 386 unique miRNAs were altered. Based on miRNA expression and fold-change, the target genes of 76 selected miRNAs were further analyzed using gene interaction networks and pathway enrichment analysis. These miRNAs were involved in the regulation of different pathways, whose functions included apoptosis, cell proliferation, extracellular matrix remodeling, oxidative stress and lipid metabolism. These differentially expressed miRNAs included let-7 family, miR-29b-3p, miR-378-3/5p, miR-351-3p, miR-664-3p, miR-455-3p, miR-298-3p, miR-702-5p, miR-128-1-5p, miR-671 and miR-421-5p. The present data indicated that global wide miRNA profiling in Dox-induced cardiomyocytes may provide a novel mechanistic insight into understanding Dox-induced heart failure and cardiotoxicity, as well as novel biomarkers and therapeutic targets.