Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNAi screening, we ...identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific gene expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETis) induced BPDCN apoptosis, which was attributable to disruption of a BPDCN-specific transcriptional network controlled by TCF4-dependent super-enhancers. BETis retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy.
•The E-box transcription factor TCF4 is a lineage-survival oncogene in BPDCN•BET inhibitors are highly toxic to BPDCNs, both in vitro and in vivo•A druggable TCF4/BRD4 transcriptional network sustains malignancy in BPDCN•BET inhibitors should be explored for the clinical management of BPDCN
Ceribelli et al. use a combination of RNAi and small-molecule screening to identify TCF4 as a crucial transcriptional regulator required for maintenance of blastic plasmacytoid dendritic cell neoplasm (BPDCN) and show that bromodomain inhibitors are potential therapeutics for BPDCN, through targeting of TCF4.
In order to deepen the health system reform and improve the mechanism for the formation of drug prices, in January 2019, the General Office of the State Council of the People's Republic of China ...issued the "National centralized drug purchasing and using pilot program", selected 11 cities in mainland China to carry out "4+7" city drug volume based purchasing pilot work. This paper introduces the specific implementation plan, organizational structure and drug selection process of China's "4+7" city drug volume-based purchasing pilot work, and expounds the initial effects, existing problems and policy development after the implementation of the policy. After the implementation of the policy, the prices of 25 selected drugs were significantly lower, compared with the minimum purchase price of the same drugs in 11 pilot cities in 2017, the average drop was 52%. After the pilot scope was extended to the nation, compared with the minimum purchase price of the Union in 2018, the proposed price of the 25 drugs have an average price drop of 59%, compared with the selected price of the "4+7" pilot cities, the average price drop was 25%, and the price of drugs dropped further. By the end of August 2019, the implementation progress of 25 selected drugs in the "4+7" city drug volume-based purchasing was better than expected, the burden of patients’ drug expenses was reduced, and the pilot work was beginning to bear fruit. The long-term influence and effect of the "4+7" city drug volume-based purchasing and policy implementation after the expansion needs to be further observed.
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•ZJME is rich in multi-antioxidant active substances.•ZJME delayed the process of senescence of C. elegans.•ZJME enhanced antioxidant capacity of N2 C. elegans.•ZJME activated the ...AMPK and signaling pathway while inhibiting IIS pathway to anti-aging.
Zizyphus jujuba Mill is a typical food-medicine homology in China, and the adage of “three jujubes a day, longevity” highlights its potential antiaging properties. However, its antiaging effect and mechanism have been poorly explored. In this study, Caenorhabditis elegans was utilized to investigate the antiaging effects and underlying mechanisms of the active components of jujube water extract (ZJME). We discovered that ZJME is rich in polysaccharides (264.15 mg/g), polyphenols (9.29 mg/g), cAMP and other components with antioxidant effects. ZJME significantly prolonged the average and maximum lifespan (31 % and 14 %) of nematodes under oxidative stress conditions. ZJME reduced the release of ROS and RNS by 44 % and 22 %, and increased the activity of the antioxidant enzymes SOD by 18 % (P < 0.01) and CAT by 55 % (P < 0.05). qRT-PCR analysis revealed that ZJME regulated the AMPK and MAPK pathway while inhibiting the IIS pathway to enhance the antioxidant defense system.
A hospital-based health technology assessment (HB-HTA) can provide the evidence needed to inform clinical decisions at the administrative level. With the implementation of a new round of medical and ...health care system reforms in China, such as the abolition of medical mark-ups, adoption of modern hospital management systems, reform of diagnosis related groups (DRGs) payment, and performance evaluations for public hospitals, medical institutions increasingly need HB-HTA. The development of HB-HTA in China can be divided into three phases: An initiation phase (2005–2014), a preliminary exploratory phase (2015–2017), and a rapid development phase (2018–present). HB-HTA has been used to manage medical consumables, medical devices, and medicines, but there are still problems and challenges in terms of concept recognition, the mode of development, and limited professionals and data. To promote and use HB-HTA in developing countries, we have identifies the development paths and recommendations for implementation based on a case study in China, which can be summarized as follows: enhancing the top-level design of HB-HTA, formulating HB-HTA guidelines, further promoting the main ideas of HB-HTA, concentrating on the training of evaluation personnel, establishing an HB-HTA network and paying attention to the flexibility of HB-HTA in the application process, and multi- stakeholder participation.
Pecan (
) nuts are delicious and rich in unsaturated fatty acids, which are beneficial for human health. Their yield is closely related to several factors, such as the ratio of female and male ...flowers. We sampled and paraffin-sectioned female and male flower buds for one year and determined the stages of initial flower bud differentiation, floral primordium formation, and pistil and stamen primordium formation. We then performed transcriptome sequencing on these stages. Our data analysis suggested that FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 play a role in flower bud differentiation.
was highly expressed in the early stage of female flower buds and may play a role in regulating flower bud differentiation and flowering time. Genes such as
and
were expressed during male flower bud development.
belongs to the NF-Y transcription factor family and may initiate downstream events leading to floral transformation.
promoted the transformation of leaf buds to flower buds.
may have been involved in the establishment of floral meristem characteristics and the determination of floral organ characteristics. Our results lay a foundation for the control and subsequent regulation of female and male flower bud differentiation and yield improvement.
Liver cancer (LCa) is one of the most common malignancies. Western medicine is the main treatment strategy of LCa, but it has not achieved the ideal therapeutic effect. Traditional Chinese Medicines ...(TCMs) have a wide range of biological effects, lots of evidence suggests that they may kill tumors by regulating the tumor microenvironment and enhancing the immune system.
The purpose of this research is to explore the medication rules of TCMs in treating LCa and excavate the potential TCMs for LCa.
We combined genes associated with the MAPK, PI3K/Akt, and mTOR signaling pathways, as well as differentially expressed genes of LCa from the TCGA database, to determine 12 prospective core targets by building a prognostic model. We added 18 previously published LCa core targets to create a list of key targets. GO and KEGG analyses were used to validate the rationality of the key targets. The reliability of the corresponding relationships between targets and compounds was verified by molecular docking. The targets-compounds-herbs network was constructed and topologically analyzed to obtain potential herbs for LCa. The nature, flavor and meridian tropism of the herbs were analyzed to explore the rule of TCMs in the treatment of LCa.
We obtained 30 potential targets including BRCA1, STMN1, MECOM, ITGB5 and SKP2. A total of 115 candidate compounds including resveratrol, quercetin, epigallocatechin gallate, estradiol and curcumin, and 1182 candidate herbs, including Jinyinhua, Gouguye, Tufuling, Huzhang, Jishiteng, Nvzhenzi, Sangbaipi and Qianhu were obtained. The vast majority of LCa's core targets, compounds and herbs we obtained have been verified by previous studies. Among the potential herbs, the categories of clearing heat and detoxifying, activating blood and dissolving stasis, and strengthening the spleen and benefiting the qi accounted for a high percentage. The herbs against LCa are mainly bitter, pungent, sweet in flavor, warm, cold, and mild in nature, and are mainly distributed in the liver, stomach, and lung meridians.
Some of the potential herbs we obtained like Jinyinhua, Gouguye, Tufuling, Huzhang and Qianhu have been proved to be effective for LCa, while some of them like Jishiteng, Nvzhenzi and Sangbaipi have been shown to have a protective effect on the liver. The potential herbs have not been widely and deeply used and need to be further explored. The combination of network pharmacology and data mining provides novel approaches to the screening and exploitation of TCM.
A novel angiotensin-converting enzyme (ACE) inhibitory peptide ser-ala-ser-val-ile-pro-val-ser-ala-val-arg-ala (SASVIPVSAVRA) was purified and identified from yak bone by Electrospray Ionization-Time ...of Flight-Mass Spectrometry (ESI-TOF-MS). Results
in vitro
showed that the peptide exhibited strong ACE inhibition activities with an IC
50
of 54.22 μM. Molecular docking results showed the binding between the peptide SASVIPVSAVRA and ACE mainly driven by van der Waals forces, hydrogen bonds and metal receptor. Interestingly, the ACE inhibition activities of the peptide increased about 19% after digestion, but none of its metabolites showed stronger activity than it. The
in vivo
experiment showed that the antihypertensive effect of peptide SASVIPVSAVRA at dose of 30 mg/kg is nearly equal to Captopril at dose of 10 mg/kg to spontaneously hypertensive rats (SHRs). The antihypertensive effect mechanism of SASVIPVSAVRA should be further studied through plasma metabolomics and bioanalysis. Structure analysis of amino acids and peptides produced during digestion may help better understand the antihypertensive effect of peptides.
19F NMR has been extensively used in simultaneous analysis of multicomponent due to its 100% natural isotope abundance, high NMR-sensitivity, and wide-range chemical shifts. The solvent effects are ...usually observed in NMR spectroscopy and cause large changes in 19F chemical shifts. Herein, we propose that the simultaneous analysis of a complex mixture can be achieved using solvent effects via 19F NMR spectroscopy, such as a mixture solution of amino acids (AAs). AAs are not only cell-signaling molecules, but are also considered as biomarkers of some diseases. Hence, the analysis of AAs is important for human health and the diagnosis of diseases. In this work, the key to the success of sensing 19 biogenic AAs is the use of 2-fluorobenzaldehyde (2FBA) as a highly sensitive derivatizing agent and solvent effects to produce distinguishable 19F NMR signals. As a result, the resolution of 19F NMR spectroscopy of multiple 2FBA-labeled AAs is obviously higher than other methods based on 19F NMR. Moreover, 14 and 18 AAs can be satisfactorily differentiated and unambiguously identified in different complicated media supporting the growth of mammalian cells. Furthermore, quantification of the concentration of AAs can be made, and the limit of detection reaches 10 μM. Our work provides new insights into the simultaneous analysis of a multicomponent mixture based on solvent effects by 19F NMR spectroscopy.
F NMR has been extensively used in simultaneous analysis of multicomponent due to its 100% natural isotope abundance, high NMR-sensitivity, and wide-range chemical shifts. The solvent effects are ...usually observed in NMR spectroscopy and cause large changes in
F chemical shifts. Herein, we propose that the simultaneous analysis of a complex mixture can be achieved using solvent effects
F NMR spectroscopy, such as a mixture solution of amino acids (AAs). AAs are not only cell-signaling molecules, but are also considered as biomarkers of some diseases. Hence, the analysis of AAs is important for human health and the diagnosis of diseases. In this work, the key to the success of sensing 19 biogenic AAs is the use of 2-fluorobenzaldehyde (2FBA) as a highly sensitive derivatizing agent and solvent effects to produce distinguishable
F NMR signals. As a result, the resolution of
F NMR spectroscopy of multiple 2FBA-labeled AAs is obviously higher than other methods based on
F NMR. Moreover, 14 and 18 AAs can be satisfactorily differentiated and unambiguously identified in different complicated media supporting the growth of mammalian cells. Furthermore, quantification of the concentration of AAs can be made, and the limit of detection reaches 10 μM. Our work provides new insights into the simultaneous analysis of a multicomponent mixture based on solvent effects by
F NMR spectroscopy.
ObjectivesThere is a tendency to pursue higher-level hospitalisation services in China, especially for internal migrants. This study aims to investigate the choices of hospitalisation services among ...internal migrants, and evaluate the association between social health insurance and hospitalisation choices.MethodsData were from a 2014 nationally representative cross-sectional sample of internal migrants aged 15–59 years in China. Descriptive analyses were used to perform the distribution of healthcare facility levels for hospitalisation services, and multinomial logistic regression was applied to examine the association between social health insurance and hospitalisation choices.ResultsOf the 6121 inpatient care users, only 11.50% chose the primary healthcare facilities for hospitalisation services, 44.91% chose the secondary hospitals and 43.59% preferred the tertiary hospitals. The choices presented large regional variations across the country. Compared with the uninsured, social health insurance had no statistically significant effect on patient choices of healthcare facility levels among internal migrants in China, whereas socioeconomic status was positively associated with the choices.ConclusionsSocial health insurance had little influence on the hospital choice among the internal migrants. Thus, social health insurance should be consolidated and portable to enhance the proper incentive of health insurance on healthcare seeking behaviours.
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