Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such a...Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and leukemia.However,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and cataract.These notorious side effects seriously compromise patients'quality of life,especially in patients with chronic diseases.Therefore,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention.Among them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising strategy.In this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so on.Besides,we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs.This review is expected to be helpful for the research and development of novel GCs and prodrugs.展开更多
Pebble bed reactors use cycling scheme of spherical fuel elements relying on fuel elements cycling system (FECS). The structure and control logic of FECS are very complex. Each control link has strict requirements on ...Pebble bed reactors use cycling scheme of spherical fuel elements relying on fuel elements cycling system (FECS). The structure and control logic of FECS are very complex. Each control link has strict requirements on time and sequence. This increases the difficulties of description and analysis. In this paper, timed places control Petri nets (TPCPN) is applied for the modeling of FECS. On this basis the simulation of two important processes, namely uploading fuel elements into the core for the first time and emptying the core is finished by simulation software Arena. The results show that as TPCPN is able to describe different kinds of logic relationship and has time properties and control properties, it’s very suitable for the modeling and analysis of FECS.展开更多
Wilms tumor (WT) is the most common childhood kidney cancer. Although WT is largely curable, current treatments fail in up to 15 percent of patients. Moreover, survivors suffer from the complications and late effects ...Wilms tumor (WT) is the most common childhood kidney cancer. Although WT is largely curable, current treatments fail in up to 15 percent of patients. Moreover, survivors suffer from the complications and late effects of the aggressive treatments. Thus, there is a critical need to improve our understanding of tumorigenesis to develop novel therapies to reduce the treatment burden while maintaining excellent survival rates. WT is believed to arise from the immature kidney cells, nephron progenitor cells (NPCs), which have failed to differentiate properly. Previous studies revealed that Wilms cells share a transcriptional and epigenetic landscape with normal renal stem cells.1 Although several studies have shown the positive associations between WT in children and embryonic exposure to adverse environments, the underlying mechanisms remain unknown. Altered epigenetics is central to oncogenesis in many pediatric cancers. The critical contribution of epigenetic dysregulation to pediatric tumors provides a compelling rationale for the therapeutic potential of epigenetic drugs. Histone deacetylases (HDACs) and Enhancer of Zeste Homolog 2 (EZH2, a histone H3K27 methyltransferase), have been demonstrated to play a critical role in self-renewal and differentiation of mouse NPCs.2,3 In addition, altered expression and mutations of HDACs and EZH2 have been linked to many human cancers, including WT. Thus, they are among the most promising therapeutic targets for cancer treatment. We reasoned that WT would result from the unrestrained proliferation of progenitor cells due to overactive HDAC1/2 (HDAC1 and HDAC2), and EZH2. We tested this hypothesis by analyzing a clinical specimen received from the left kidney tumor of an 11-year-old male patient diagnosed with WT and four other human WT specimens. We have the approval from Tulane Human Research Protection Office & Institutional Review Boards (Study number: 2019–623) to study WT specimens. The tumor (9.5 cm × 8 cm × 7.5 cm) is classified as favorable for the histology of indeterminate cell tumors. As shown in Figure 1A, the tumor exhibits a biphasic pattern with significant blastemal component admixed with stromal component. No significant epithelial component is present. The blastema represents the undifferentiated and malignant component, consisting of small round blue cells with overlapping nuclei and brisk mitotic activity. The blastemal component shows somewhat a basaloid growth pattern. The stromal component is also prominent and includes hypercellular undifferentiated mesenchymal cells.展开更多
Coix lacryma-jobi,a plant species closely related to Zea and Sorghum,is an important food and medicinal crop in Asia.However,no reference genome of this species has been reported,and its exact phylogeny within the And...Coix lacryma-jobi,a plant species closely related to Zea and Sorghum,is an important food and medicinal crop in Asia.However,no reference genome of this species has been reported,and its exact phylogeny within the Andropogoneae remains unresolved.Here,we generated a high-quality genome assembly of coix comprising～1.73 Gb with 44485 predicted protein-coding genes.We found coix to be a typical diploid plant with an overall 1-to-1 syntenic relationship with the Sorghum genome,despite its drastic genome expansion(～2.3-fold)due mainly to the activity of transposable elements.Phylogenetic analysis revealed that coix diverged with sorghum～10.41 million years ago,which was～1.49 million years later than the divergence between sorghum and maize.Resequencing of 27 additional coix accessions revealed that they could be unambiguously separated into wild relatives and cultivars,and suggested that coix experienced a strong genetic bottleneck,resulting in the loss of about half of the genetic diversity during domestication,even though many traits have remained undomesticated.Our data not only provide novel comparative genomic and evolutionary insights into the Andropogoneae lineage,but also an important resource that will greatly benefit molecular breeding of this important crop.展开更多
Objective To evaluate the prognosis values of systemic immune-inflammation index(SII)in non-chronic cerebral venous sinus thrombosis(CVST).Methods patients with CVST,admitted to the First Affiliated Hospital of Zhengz...Objective To evaluate the prognosis values of systemic immune-inflammation index(SII)in non-chronic cerebral venous sinus thrombosis(CVST).Methods patients with CVST,admitted to the First Affiliated Hospital of Zhengzhou University,were retrospectively identified from January 2013 to December 2018.We selected patients in acute/subacute phase from database.Functional outcomes of patients were evaluated with the modified Rankin Scale(mRS)-mRS 3-6 as poor outcomes and mRS 6 as death.The overall survival time was defined as the date of onset to the date of death or last follow-up date.Survival analysis was described by the Kaplan-Meier curve and Cox regression analysis.Multivariate logistic regression analysis assessed the relationship between SII and poor functional outcome.The area under the Receiver Operating Curve curve(AUC)was estimated to evaluate the ability of SII in prediction.Results A total of 270 patients were included and their duration of follow-up was 22 months(6-66 months),of whom 31 patients had poor outcomes and 24 patients dead.Cox regression analysis showed that SII(HR=1.304,95%CI:1.101 to 1.703,p=0.001)was a predictor of death in non-chronic CVST.Patients with higher SII presented lower survival rates(p=0.003).The AUC of SII was 0.792(95%CI:0.695 to 0.888,p=0.040)with a sensitivity of 69.6%and specificity of 80.1%.Subgroups analysis demonstrated that SII was an important predictor of poor outcomes in male(OR=1.303,95%CI:1.102 to 1.501,p=0.011)and pregnancy/puerperium female(OR=1.407,95%CI:1.204 to 1.703,p=0.034).Conclusions SII was a potential predictor in the poor prognosis of patients with acute/subacute CVST,especially in male and pregnancy/puerperium female.展开更多
基金supported by the National Natural Science Foundation of China[82172086]National Key R&D Program of China[2020YFE0201700]+2 种基金Shenyang Science and Technology Talent Support Program[RC210447]Career Development Program for Young and Middle-aged Teachers of Shenyang Pharmaceutical University[ZQN2019004]“Dual Service”Program of University in Shenyang。
文摘Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and leukemia.However,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and cataract.These notorious side effects seriously compromise patients'quality of life,especially in patients with chronic diseases.Therefore,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention.Among them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising strategy.In this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so on.Besides,we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs.This review is expected to be helpful for the research and development of novel GCs and prodrugs.
文摘Pebble bed reactors use cycling scheme of spherical fuel elements relying on fuel elements cycling system (FECS). The structure and control logic of FECS are very complex. Each control link has strict requirements on time and sequence. This increases the difficulties of description and analysis. In this paper, timed places control Petri nets (TPCPN) is applied for the modeling of FECS. On this basis the simulation of two important processes, namely uploading fuel elements into the core for the first time and emptying the core is finished by simulation software Arena. The results show that as TPCPN is able to describe different kinds of logic relationship and has time properties and control properties, it’s very suitable for the modeling and analysis of FECS.
基金supported by the American Heart Association(No.17SDG33660072)the Louisiana Board of Regents Support Fund(No.LEQSF-RD-A-18)to Dr.Hongbing Liu.
文摘Wilms tumor (WT) is the most common childhood kidney cancer. Although WT is largely curable, current treatments fail in up to 15 percent of patients. Moreover, survivors suffer from the complications and late effects of the aggressive treatments. Thus, there is a critical need to improve our understanding of tumorigenesis to develop novel therapies to reduce the treatment burden while maintaining excellent survival rates. WT is believed to arise from the immature kidney cells, nephron progenitor cells (NPCs), which have failed to differentiate properly. Previous studies revealed that Wilms cells share a transcriptional and epigenetic landscape with normal renal stem cells.1 Although several studies have shown the positive associations between WT in children and embryonic exposure to adverse environments, the underlying mechanisms remain unknown. Altered epigenetics is central to oncogenesis in many pediatric cancers. The critical contribution of epigenetic dysregulation to pediatric tumors provides a compelling rationale for the therapeutic potential of epigenetic drugs. Histone deacetylases (HDACs) and Enhancer of Zeste Homolog 2 (EZH2, a histone H3K27 methyltransferase), have been demonstrated to play a critical role in self-renewal and differentiation of mouse NPCs.2,3 In addition, altered expression and mutations of HDACs and EZH2 have been linked to many human cancers, including WT. Thus, they are among the most promising therapeutic targets for cancer treatment. We reasoned that WT would result from the unrestrained proliferation of progenitor cells due to overactive HDAC1/2 (HDAC1 and HDAC2), and EZH2. We tested this hypothesis by analyzing a clinical specimen received from the left kidney tumor of an 11-year-old male patient diagnosed with WT and four other human WT specimens. We have the approval from Tulane Human Research Protection Office & Institutional Review Boards (Study number: 2019–623) to study WT specimens. The tumor (9.5 cm × 8 cm × 7.5 cm) is classified as favorable for the histology of indeterminate cell tumors. As shown in Figure 1A, the tumor exhibits a biphasic pattern with significant blastemal component admixed with stromal component. No significant epithelial component is present. The blastema represents the undifferentiated and malignant component, consisting of small round blue cells with overlapping nuclei and brisk mitotic activity. The blastemal component shows somewhat a basaloid growth pattern. The stromal component is also prominent and includes hypercellular undifferentiated mesenchymal cells.
基金supported by the National Key Research and Development Program(2016YFD0101003)of China and the National Natural Science Foundation of China(91735305,91435206,91635303-3,31701430 and 31421005).
文摘Coix lacryma-jobi,a plant species closely related to Zea and Sorghum,is an important food and medicinal crop in Asia.However,no reference genome of this species has been reported,and its exact phylogeny within the Andropogoneae remains unresolved.Here,we generated a high-quality genome assembly of coix comprising～1.73 Gb with 44485 predicted protein-coding genes.We found coix to be a typical diploid plant with an overall 1-to-1 syntenic relationship with the Sorghum genome,despite its drastic genome expansion(～2.3-fold)due mainly to the activity of transposable elements.Phylogenetic analysis revealed that coix diverged with sorghum～10.41 million years ago,which was～1.49 million years later than the divergence between sorghum and maize.Resequencing of 27 additional coix accessions revealed that they could be unambiguously separated into wild relatives and cultivars,and suggested that coix experienced a strong genetic bottleneck,resulting in the loss of about half of the genetic diversity during domestication,even though many traits have remained undomesticated.Our data not only provide novel comparative genomic and evolutionary insights into the Andropogoneae lineage,but also an important resource that will greatly benefit molecular breeding of this important crop.
基金supported by the Science and Technology Department of the Henan Province grant number(No.152102310058)the National Natural Science Foundation of China grant number(Nos.81530037).
文摘Objective To evaluate the prognosis values of systemic immune-inflammation index(SII)in non-chronic cerebral venous sinus thrombosis(CVST).Methods patients with CVST,admitted to the First Affiliated Hospital of Zhengzhou University,were retrospectively identified from January 2013 to December 2018.We selected patients in acute/subacute phase from database.Functional outcomes of patients were evaluated with the modified Rankin Scale(mRS)-mRS 3-6 as poor outcomes and mRS 6 as death.The overall survival time was defined as the date of onset to the date of death or last follow-up date.Survival analysis was described by the Kaplan-Meier curve and Cox regression analysis.Multivariate logistic regression analysis assessed the relationship between SII and poor functional outcome.The area under the Receiver Operating Curve curve(AUC)was estimated to evaluate the ability of SII in prediction.Results A total of 270 patients were included and their duration of follow-up was 22 months(6-66 months),of whom 31 patients had poor outcomes and 24 patients dead.Cox regression analysis showed that SII(HR=1.304,95%CI:1.101 to 1.703,p=0.001)was a predictor of death in non-chronic CVST.Patients with higher SII presented lower survival rates(p=0.003).The AUC of SII was 0.792(95%CI:0.695 to 0.888,p=0.040)with a sensitivity of 69.6%and specificity of 80.1%.Subgroups analysis demonstrated that SII was an important predictor of poor outcomes in male(OR=1.303,95%CI:1.102 to 1.501,p=0.011)and pregnancy/puerperium female(OR=1.407,95%CI:1.204 to 1.703,p=0.034).Conclusions SII was a potential predictor in the poor prognosis of patients with acute/subacute CVST,especially in male and pregnancy/puerperium female.
