A COMPASS histone H3K4 trimethyltransferase pentamer transactivates drought tolerance and growth/biomass production in Populus trichocarpa.

Histone H3 lysine-4 trimethylation (H3K4me3) activating drought-responsive genes in plants for drought adaptation has long been established, but the underlying regulatory mechanisms are unknown. Here, using yeast two-hybrid, bimolecular fluorescence complementation, biochemical analyses, transient and CRISPR-mediated transgenesis in Populus trichocarpa, we unveiled in this adaptation a regulatory interplay between chromatin regulation and gene transactivation mediated by an epigenetic determinant, a PtrSDG2-1-PtrCOMPASS (complex proteins associated with Set1)-like H3K4me3 complex, PtrSDG2-1-PtrWDR5a-1-PtrRbBP5-1-PtrAsh2-2 (PtrSWRA). Under drought conditions, a transcription factor PtrAREB1-2 interacts with PtrSWRA, forming a PtrSWRA-PtrAREB1-2 pentamer, to recruit PtrSWRA to specific promoter elements of drought-tolerant genes, such as PtrHox2, PtrHox46, and PtrHox52, for depositing H3K4me3 to promote and maintain activated state of such genes for tolerance. CRISPR-edited defects in the pentamer impaired drought tolerance and elevated expression of PtrHox2, PtrHox46, or PtrHox52 improved the tolerance as well as growth in P. trichocarpa. Our findings revealed the identity of the underlying H3K4 trimethyltransferase and its interactive arrangement with the COMPASS for catalysis specificity and efficiency. Furthermore, our study uncovered how the H3K4 trimethyltransferase-COMPASS complex is recruited to the effector genes for elevating H3K4me3 marks for improved drought tolerance and growth/biomass production in plants.

Efficacy of artificial intelligence in reducing miss rates of GI adenomas, polyps, and sessile serrated lesions: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The aim of this study was to determine if utilization of artificial intelligence (AI) in the course of endoscopic procedures can significantly diminish both the adenoma miss rate (AMR) and the polyp miss rate (PMR) compared with standard endoscopy. METHODS: We performed an extensive search of various databases, encompassing PubMed, Embase, Cochrane Library, Web of Science, and Scopus, until June 2023. The search terms used were artificial intelligence, machine learning, deep learning, transfer machine learning, computer-assisted diagnosis, convolutional neural networks, gastrointestinal (GI) endoscopy, endoscopic image analysis, polyp, adenoma, and neoplasms. The main study aim was to explore the impact of AI on the AMR, PMR, and sessile serrated lesion miss rate. RESULTS: A total of 7 randomized controlled trials were included in this meta-analysis. Pooled AMR was markedly lower in the AI group versus the non-AI group (pooled relative risk [RR], .46; 95% confidence interval [CI], .36-.59; P < .001). PMR was also reduced in the AI group in contrast with the non-AI control (pooled RR, .43; 95% CI, .27-.69; P < .001). The results showed that AI decreased the miss rate of sessile serrated lesions (pooled RR, .43; 95% CI, .20 to .92; P < .05) and diminutive adenomas (pooled RR, .49; 95% CI, .26-.93) during endoscopy, but no significant effect was observed for advanced adenomas (pooled RR, .48; 95% CI, .17-1.37; P = .17). The average number of polyps (Hedges' g = -.486; 95% CI, -.697 to -.274; P = .000) and adenomas (Hedges' g = -.312; 95% CI, -.551 to -.074; P = .01) detected during the second procedure also favored AI. However, AI implementation did not lead to a prolonged withdrawal time (P > .05). CONCLUSIONS: This meta-analysis suggests that AI technology leads to significant reduction of miss rates for GI adenomas, polyps, and sessile serrated lesions during endoscopic surveillance. These results underscore the potential of AI to improve the accuracy and efficiency of GI endoscopic procedures.

Acetylene Semihydrogenation over Pd-Bi Intermetallic Compounds: A DFT Combined with Microkinetic Modeling Study.

Acetylene semihydrogenation is an important process both theoretically and experimentally. Pure Pd catalysts usually suffer from limited selectivity for ethylene products and poor stability. Pd-Bi bimetallic compounds are synthesized and show not only excellent catalytic performance but also remarkable long-term stability. However, the detailed mechanism is still unclear. In this paper, the acetylene semihydrogenation mechanism on Pd(100), Pd3Bi1(100), and Pd1Bi1(100) is studied by density functional theory (DFT) calculation and microkinetic modeling. Adding Bi causes the surface d-band center (εd) to move to a lower energy, and the adsorption strength of the intermediate becomes weaker. Besides, ethylidyne (CCH3) formation becomes more difficult on the Pd-Bi alloy due to the lack of continuous surface Pd atoms. As a spectator, CCH3 deactivates the Pd and Pd-Bi alloys by a steric effect. However, the selectivity for ethylene on the Pd-Bi alloy is still high because of the weakly bonded ethylene. We found the relationship between εd and the catalysts' activity and selectivity. This study may supply some clues for the design of selective hydrogenation catalysts.

A Simple and Universal Approach to Synthesizing Multi-Confined Carbon Dots with Thermally Activated Delayed Fluorescence.

Afterglow materials possess the remarkable capability to harness the energy and subsequently emit light after irradiation is turned off. Owing to their extraordinary ultralong lifetime, afterglow materials have garnered significant interest across various domains such as sensing, optoelectronics, bioimaging, and information encryption. However, these materials typically exhibit temperature sensitivity, rendering their afterglow emission susceptible to efficient quenching at room temperature. Consequently, this study presents herein a straightforward, simple, and universal approach for synthesizing metal-free carbon dots (CDs) endowed with thermally activated delayed fluorescence (TADF) characteristics at room temperature. In this study, TADF-CDs were simply synthesized by pyrolyzing boronic acid (BA) and urea at 500 ℃ for 3 h. Benefiting from the multi-confined effects facilitated by the robust structure of BA matrix, in conjunction with the co-doped heteroatoms of nitrogen and boron, the resultant TADF-CDs manifest remarkably prolonged afterglow TADF emission, characterized by a calculated lifetime of 184.64 ms; moreover, the blue afterglow emission remains perceptible to the naked eye for more than 6 s. The attributes of TADF-CDs were comprehensively elucidated through rigorous characterization, and the universality of the approach was corroborated through experimentation involving fourteen control CDs. Leveraging their distinctive TADF attributes, the prepared TADF-CDs were subsequently employed in advanced applications such as anti-counterfeiting and information encryption.

Understanding three approaches to reporting sudden unexpected infant death in the USA.

INTRODUCTION: In the USA each year, there are approximately 3400 sudden unexpected infant (<1 year of age) deaths (SUID) which occur without an obvious cause before an investigation. SUID includes the causes of death (COD) undetermined/unknown, sleep-related suffocation/asphyxia and sudden infant death syndrome (SIDS); these are often called SUID subtypes. Three common ways SUID subtypes are grouped (SUID subtype groups) include International Classification of Diseases (ICD) Codes, SUID Case Registry Categories or Child Death Review (CDR)-Assigned Causes. These groups are often used to monitor SUID trends and characteristics at the local, state and national levels. We describe and compare the characteristics of these three SUID subtype groups. DISCUSSION: SUID subtype groups are distinct and not directly interchangeable. They vary in purpose, strengths, limitations, uses, history, data years available, population coverage, assigning entity, guidance documentation and information available to assign subtypes. CONCLUSION: Making informed decisions about which SUID subtype group to use is important for reporting statistics, increasing knowledge of SUID epidemiology and informing prevention strategies.

Single-cell RNA Sequencing Demonstrates the Heterogeneity of Different Molecular Subtypes in Gastric Cancer.

Gastric cancer is a disease with high molecular and phenotypic heterogeneity. We integrated 119,878 cells from different molecular subtypes of gastric cancer and conducted comprehensive analysis. We found that patients with different molecular subtypes of gastric cancer showed significantly different cell composition heterogeneity, and the proportion of plasma cells was higher in GS tumors. After that, we constructed subtype-specific lncRNA-gene regulatory networks and identified subtype-specific lncRNA-related biological functions and pathways. Our study found that MALAT1-CTNNB1 regulatory pairs existed in CIN subtype, XIST-KLF2 regulatory pairs existed in GS subtype, and KCNQ1OT1-CCND2 regulatory pairs existed in MSI subtype. Next, we identified subtype-specific lncRNAs associated with prognosis. Our study found that NEAT1 could be used as prognostic factors for CIN tumors, and MALAT1 and XIST could be used as prognostic factors for GS tumors. In addition, we characterized the interactions between tumor cells and tumor microenvironment cells in different molecular subtypes of gastric cancer. In conclusion, we revealed the heterogeneity among different TCGA molecular subtypes of gastric cancer at the single-cell level, and identified the subtype-specific lncRNAs associated with prognosis. Our study may contribute to the in-depth understanding of the heterogeneity of gastric cancer and the prediction of patient prognosis.

Microglia homeostasis mediated by epigenetic ARID1A regulates neural progenitor cells response and leads to autism-like behaviors.

Microglia are resident macrophages of the central nervous system that selectively emerge in embryonic cortical proliferative zones and regulate neurogenesis by altering molecular and phenotypic states. Despite their important roles in inflammatory phagocytosis and neurodegenerative diseases, microglial homeostasis during early brain development has not been fully elucidated. Here, we demonstrate a notable interplay between microglial homeostasis and neural progenitor cell signal transduction during embryonic neurogenesis. ARID1A, an epigenetic subunit of the SWI/SNF chromatin-remodeling complex, disrupts genome-wide H3K9me3 occupancy in microglia and changes the epigenetic chromatin landscape of regulatory elements that influence the switching of microglial states. Perturbation of microglial homeostasis impairs the release of PRG3, which regulates neural progenitor cell self-renewal and differentiation during embryonic development. Furthermore, the loss of microglia-driven PRG3 alters the downstream cascade of the Wnt/ß-catenin signaling pathway through its interaction with the neural progenitor receptor LRP6, which leads to misplaced regulation in neuronal development and causes autism-like behaviors at later stages. Thus, during early fetal brain development, microglia progress toward a more homeostatic competent phenotype, which might render neural progenitor cells respond to environmental cross-talk perturbations.

MacroH2A1.2 deficiency leads to neural stem cell differentiation defects and autism-like behaviors.

The development of the nervous system requires precise regulation. Any disturbance in the regulation process can lead to neurological developmental diseases, such as autism and schizophrenia. Histone variants are important components of epigenetic regulation. The function and mechanisms of the macroH2A (mH2A) histone variant during brain development are unknown. Here, we show that deletion of the mH2A isoform mH2A1.2 interferes with neural stem cell differentiation in mice. Deletion of mH2A1.2 affects neurodevelopment, enhances neural progenitor cell (NPC) proliferation, and reduces NPC differentiation in the developing mouse brain. mH2A1.2-deficient mice exhibit autism-like behaviors, such as deficits in social behavior and exploratory abilities. We identify NKX2.2 as an important downstream effector gene and show that NKX2.2 expression is reduced after mH2A1.2 deletion and that overexpression of NKX2.2 rescues neuronal abnormalities caused by mH2A1.2 loss. Our study reveals that mH2A1.2 reduces the proliferation of neural progenitors and enhances neuronal differentiation during embryonic neurogenesis and that these effects are at least in part mediated by NKX2.2. These findings provide a basis for studying the relationship between mH2A1.2 and neurological disorders.

M supported on Al-defective Al2-δO3 (M = Fe, Co, Ni, Cu, Ag, Au) as catalysts for acetylene semi-hydrogenation: a theoretical perspective.

Semi-hydrogenation of acetylene is of great importance for both industry and academia. High prices and limited supplements of noble metals leave room for developing base metal catalysts. Experiments revealed the atomically dispersed Cu supported by Al2O3 with excellent long-term stability and high ethylene selectivity, but the physical nature has rarely been investigated theoretically. DFT calculations and microkinetic modeling revealed that the surface OH species could stabilize Cu1/Al2-δO3 and enhance its catalytic performance. The selectivity of ethylene formation decreases with increasing copper clusters (e.g., Cu1/Al2-δO3> Cu4/Al2-δO3> Cu8/Al2-δO3), meaning that the atomically dispersed copper may be a potential candidate for acetylene semi-hydrogenation. The structures of a series of single site catalysts M1/Al2-δO3 (M = Fe, Co, Ni, Ag, Au) are similar to that of Cu1/Al2-δO3, but their performances in catalyzing acetylene semi-hydrogenation are different. M1/Al2-δO3 (M = Ag, Au) shows higher selectivity than Cu1/Al2-δO3, while M1/Al2-δO3 (M = Fe, Co, Ni) demonstrates a higher turnover frequency (TOF) of ethylene than Cu1/Al2-δO3. Moreover, our results indicate that the Ni1-Cu1/Al2-δO3 alloy shows both high activity and ethylene selectivity. The present results show a compensation between the reactivity and the selectivity, suggesting that alloys of VIIIB metals with IB metals like Ni1-Cu1/Al2-δO3 may be efficient candidate catalysts in acetylene selective hydrogenation.

Propofol suppresses OGD/R-induced ferroptosis in neurons by inhibiting the HIF-1α/YTHDF1/BECN1 axis.

BACKGROUND: Ischemia/reperfusion (I/R) is a pathological process that causes severe damage. Propofol is known to alleviate I/R-related injury; however, the exact function and underlying mechanisms are not fully understood. METHODS: Using an oxygen glucose deprivation/re-oxygenation (OGD/R) method, an in vitro I/R injury model was induced. The cell viability and the level of Fe2+, glutathione synthetase (GSH), and malondialdehyde (MDA) were evaluated using kits. Luciferase reporter gene assay, chromatin immunoprecipitation, and RNA immunoprecipitation (RIP) were used to verify the interaction between molecules. The m6A level of BECN1 mRNA was determined through methylated RIP. RESULTS: Propofol-treated OGD/R models showed reduced levels of Fe2+ and MDA, while the cell viability and the level of GSH increased. Propofol inhibited ferroptosis by down-regulating HIF-1α in OGD/R-treated HT22 cells. HIF-1α is bound to the promoter region of YTHDF1 to promote its transcription, and YTHDF1 promoted ferroptosis by stabilizing the mRNA of BECN1. The suppressive effect of propofol on OGD/R-induced ferroptosis was reversed by the overexpression of YTHDF1. CONCLUSIONS: Our study revealed that the HIF-1α/YTHDF1/BECN1 axis in OGD/R-treated HT22 cells promotes ferroptosis, and administration of propofol can inhibit this axis to avoid cell death. This study provides a novel insight for the neuroprotective function of propofol.

A Review of Dual-Emission Carbon Dots and Their Applications.

Carbon dots (CDs), as a rising star among fluorescent nanomaterials with excellent optical properties and fascinating dual-emission characteristics, have attracted increasing attention in sensing, bio-imaging, drug delivery, and so on. The synthesis of dual-emission CDs (DE-CDs) and the establishment of ratiometric fluorescence sensors can effectively diminish background interference and provide more accurate results than single-emission CDs. Although DE-CDs have generated increased attention in many fields, the review articles about DE-CDs are still insufficient. Therefore, we summarized the latest results and prepared this review. This review first provides an overview of the primary synthesis route and commonly used precursors in DE-CDs synthesis. Then, the photoluminescence mechanism behind the dual-emission phenomenon was discussed. Thirdly, the application of DE-CDs in metal cation detection, food safety analysis, biosensing, cell imaging, and optoelectronic devices has been extensively discussed. Finally, the main challenges and prospects for further development are presented. This review presents the latest research progress of DE-CDs synthesis and its application in ratiometric sensing; hopefully, it can help and encourage researchers to overcome existing challenges and broaden the area of DE-CDs research.

Lead dissociation and redistribution properties of actual contaminated farmland soil after long-term EKAPR treatment.

Electrokinetic-assisted phytoremediation (EKAPR) is a potential technology much affected by the metal species and accessibility to plant roots. In this study, Pb-contaminated red soil was remediated with Sedum plumbizincicola to investigate the changes in soil pH, available nutrients, dissociation and redistribution of Pb under a long-term periodic reversal direct-current electric field. This approach could effectively activate soil P, K, organic matter (OM) and Pb, without significant soil acidification; the effect was positively correlated with applied voltage. Soil Pb can be continuously dissociated, migrated, and tended to accumulate in the middle region. The maximum Pb removal rate in the anodic section of the EKAPR system was 21.4%, and the aggregation rate in middle regions was 14.4%, higher than the available Pb content of the original soil. The Pb desorption in aqueous solution increased significantly with increasing voltage, irrespective of the solution pH. At a voltage of 20 V, the Pb cumulative desorption content reached 91.1 mg kg-1 (pH = 7), which was 2.7 times than that without electric field (33.2 mg kg-1). Compared to original soil (2.80 mg kg-1) and the control (14.54 mg kg-1), the available Pb in the anode section of EKAPR system (20.66 mg kg-1) increased by 637.9% and 42.1%, respectively. These results indicated that except for the indirect influence of soil pH changes, electrodynamics can directly promote the bioavailability and dissociation of Pb at the soil-water interface. This finding provides a new perspective for further studies on the mechanism of Pb speciation evolution and accumulation changes using EKAPR.

A novel synthetic-genetic-array-based yeast one-hybrid system for high discovery rate and short processing time.

Eukaryotic gene expression is often tightly regulated by interactions between transcription factors (TFs) and their DNA cis targets. Yeast one-hybrid (Y1H) is one of the most extensively used methods to discover these interactions. We developed a high-throughput meiosis-directed yeast one-hybrid system using the Magic Markers of the synthetic genetic array analysis. The system has a transcription factor-DNA interaction discovery rate twice as high as the conventional diploid-mating approach and a processing time nearly one-tenth of the haploid-transformation method. The system also offers the highest accuracy in identifying TF-DNA interactions that can be authenticated in vivo by chromatin immunoprecipitation. With these unique features, this meiosis-directed Y1H system is particularly suited for constructing novel and comprehensive genome-scale gene regulatory networks for various organisms.

Nonfouling and Antibacterial Zwitterionic Contact Lenses Loaded with Heme-Mimetic Gallium Porphyrin for Treating Keratitis.

Antifouling and antibacterial are two critical challenges in the development of contact lenses (CLs). Herein, we presented nonfouling and antibacterial bifunctionalized CLs by encapsulating cationic heme-mimetic gallium porphyrin (Ga-CHP) into zwitterionic-elastomeric-networked (ZEN) hydrogel. Results proved that the ZEN hydrogel showed excellent abilities to resist non-specific protein adsorption, bacterial adhesion, and biofilm formation. Moreover, Ga-CHP could be sustainably released and kill >99.9% planktonic bacteria and >99.9% mature biofilms. In vivo, the symptoms of bacterial keratitis in mice were significantly alleviated after wearing the CLs for 7 days via iron-blocking and photodynamic synergistic antibacterial therapy with the help of natural sunlight. This study highlights the nonfouling and antibacterial superiority of the Ga-CHP-functional zwitterionic CLs and proposes a portable yet efficient non-antibiotic keratitis treatment strategy.

Circular RNA circPSAP functions as an efficient miR-331-3p sponge to regulate proliferation, apoptosis and bortezomib sensitivity of human multiple myeloma cells by upregulating HDAC4.

BACKGROUND: Multiple myeloma (MM) is a malignant tumor of plasma cells in the bone marrow. Circular RNAs (circRNAs) exert important activity in the tumorigenesis and chemoresistance of MM. In the current work, we sought to identify the expression, activity, and mechanism of circPSAP activity in MM. METHODS: CircPSAP, microRNA (miR)-331-3p, and histone deacetylase 4 (HDAC4) were quantified by qRT-PCR and immunoblotting assays. Cell proliferation and survival were assessed by CCK-8 assay. Cell cycle and apoptosis were detected by flow cytometry. The direct relationship between miR-331-3p and circPSAP or HDAC4 3'UTR was validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. RESULTS: CircPSAP was overexpressed in human MM and high levels of circPSAP predicted poor prognosis in MM patients. CircPSAP depletion repressed cell proliferation and promoted apoptosis and BTZ sensitivity. Mechanistically, circPSAP functioned as a miR-331-3p sponge, and circPSAP regulated cell proliferation, apoptosis and BTZ sensitivity by sponging miR-331-3p. MiR-331-3p directly targeted and inhibited HDAC4. MiR-331-3p-mediated inhibition of HDAC4 impaired cell proliferation and enhanced cell apoptosis and BTZ sensitivity. Moreover, circPSAP modulated HDAC4 expression by acting as a miR-331-3p sponge. CONCLUSION: Our findings highlight a novel mechanism, in which circPSAP functions as a miR-331-3p sponge to impact MM cell proliferation, apoptosis and BTZ sensitivity by regulating HDAC4 expression.

Time-resolved fluorescence immunoassay (TRFIA) for the simultaneous detection of hs-CRP and lipoprotein(a) in serum.

Elevated serum high-sensitivity C-reactive protein (hs-CRP) and lipoprotein(a) (Lp(a)) levels are associated with the development of native coronary atherosclerosis. We aimed to establish a new method for the simultaneous detection of hs-CRP and Lp(a) to predict the development of atherosclerosis. A one-step time-resolved fluorescence immunoassay (TRFIA) with europium(III) (Eu3+ ) or samarium(III) (Sm3+ ) labels was established, and the performance of this TRFIA (in terms of sensitivity, specificity, accuracy, and cutoff values) was evaluated using clinical serum samples and compared with those of registered kits. The sensitivity was 0.052 µg/ml for hs-CRP and 0.64 µg/ml for Lp(a). The intra-assay and inter-assay cross-reactivities (CVs) were very low, ranging from 2.05% to 4.67% for hs-CRP and from 2.42% to 6.43% for Lp(a). The CVs were very low (<0.34% and <2.65%, respectively) with five interferents. Additionally, there was a high Pearson coefficient between the present TRFIA method and the registered kits (R2 = 0.9967 and 0.9906, respectively). These data indicate that this study developed a TRFIA method that can be used for the quantitative detection of hs-CRP and Lp(a) in serum with high sensitivity, specificity, and accuracy. This TRFIA provides a new method for predicting the development of atherosclerosis.

Roles of Beclin1 protein expression in cervical cancer: a meta-analysis and bioinformatics analysis.

Beclin1 is a key regulator of a family of autophagy-related proteins. The aim of our study was to elucidate the clinicopathological and prognostic significance of Beclin1 expression which is a positive regulator of autophagy in cervical cancer. The results showed that a total of 2682 patients were enrolled in 21 case-control studies. The results showed that, as for Beclin1 expression, significant differences were found in cervical cancer vs. normal cervical tissues (p<.00001) and cancer tissues with vs. no lymph node metastasis (p<.00001); tumour diameter no less than vs. less than 4 cm (p=.001), myometrial invasion depth no less than vs. less than 1/2 and FIGO I vs. II (p=.02); relationship between Beclin1 expression and prognosis of cervical cancer (p=.03). Kaplan-Meier's plotter showed that Beclin1 expression was negative. It was associated with overall, post-progressive and distant metastatic survival. According to the Oncomine database, Beclin1 mRNA expression in cervical cancer tissues was higher than that in normal tissues. Cox multivariate showed that lymph node metastasis and TNM stage were important factors affecting the survival time of patients. Beclin1 expression can be used as an indicator of prognosis in patients, and provide methods and ideas for prevention and treatment.

[Combined anti-bitterness strategy for extremely bitter characteristics of Andrographis Herba decoction and mechanism].

Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction, and the optimal combined anti-bitterness formula was obtained. The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect. Sensory evaluation showed that mPEG_(2000)-PLLA_(2000), γ-cyclodextrin(γ-CD), and aspartame all had good anti-bitterness effect, which reduced the bitterness intensity of Andrographis Herba decoction by 0.5, 6, and 3 points, respectively. The anti-bitterness effect was superior when 0.15% mPEG_(2000)-PLLA_(2000), 1.60% γ-CD, and 0.04% aspartame were combined, and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness) to 1 point(almost no bitterness). Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups, which spontaneously combined with it and formed a physical barrier, hindering the binding of bitter components to receptors. The interaction between γ-CD and bitter components was studied. It was found that the surface area and free energy of γ-CD decreased and the dipole moment increased, indicating that γ-CD included bitter components and self-assembled to form supramolecules. Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide, and hydroxy at position 3 and 4, carbonyl at position 14, and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups. The binding free energies of aspartame to bitter receptors TAS2 R10, TAS2 R14, and TAS2 R46 were-3.21,-1.55, and-2.52 kcal·mol~(-1), respectively, indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors. The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction were 0.23% and 0.28% respectively, while after adding flavor masking excipients, the dissociation amount of andrographolide and dehydrated andrographolide in the decoction decreased to 0.13% and 0.20%, respectively. The above results show that mPEG_(2000)-PLLA_(2000) involves some bitter components into it through micellar self-assembly to reconcile the entrance bitterness, and γ-CD includes the remaining bitter components in the real solution to control the main bitter taste. Aspartame further competes to inhibit the combination of bitter components and bitter receptors, and improves the taste to be sweet. Multi-excipients combined with anti-bitterness strategy significantly reduces the free concentration of bitter substances in Andrographis Herba decoction, and optimizes the taste of the decoction.

[Material basis of stench of animal medicine: a review].

Despite the distinctive characteristics and remarkable efficacy, animal medicine is stenchy, which decreases the comp-liance of patients. At the moment, the research on the method for deodorizing animal medicines lags behind. To be specific, the components related to the odor and the basic properties transformation of the components are unclear and there is a lack of specific deodorizing method. This study aims to clarify the main components related to the stench of animal medicine, such as aldehydes, amines, trimethylamines and sulfur compounds, and their basic properties, and to explore their metabolism and transformation in vivo and in vitro, which is expected to serve as a reference for the research on deodorization of animal medicine and development of new techniques.

ALKBH5-mediated m6A-demethylation of USP1 regulated T-cell acute lymphoblastic leukemia cell glucocorticoid resistance by Aurora B.

Recent studies evidence that ubiquitin-specific proteases (USPs) are associated with the occurrence and chemoresistance of T-cell acute lymphoblastic leukemia (T-ALL). N6 -methyladenosine (m6A) demethylase AlkB homolog 5 (ALKBH5) exerts a carcinogenic effect in human cancers and improves the mRNA stability of USPs. Whether ubiquitin-specific protease 1 (USP1) controls chemoresistance of T-ALL is unknown. Our study demonstrated that USP1 expression was upregulated in glucocorticoid (GC)-resistant T-ALL patients and cells (CEM-C1). High expression of USP1 was correlated to the poor prognosis in T-ALL patients. Silencing USP1 increased CEM-C1 cell sensitivity to dexamethasone (Dex), reduced cell invasion, promoted cell apoptosis, and ameliorated glucocorticoid receptor (GR) expression. USP1 mediated T-ALL chemoresistance by interacting with and deubiquitination of Aurora B. Overexpression of USP1 reversed the amelioration effect of Aurora B inhibitor on CEM-C1 cell resistance to Dex. Mechanistically, ALKBH5 enhanced USP1 expression by reducing m6A level and mRNA stability in USP1 mRNA transcript. Downregulation of ALKBH5 reduced the levels of USP1 and Aurora B, facilitated CEM-C1 cell sensitivity to Dex, apoptosis, and GR expression, suppressed cell invasion. However, overexpression of USP1 reversed all the effects of ALKBH5 on CEM-C1 cells. In vivo results showed that tail vein injection of sh-USP1 resulted in a significant prolongation of mouse survival, suppressed tumor growth, maintained the normal weight of mice, reduced USP1 expression and facilitated GR expression. In conclusion, inhibition of ALKBH5-mediated m6A modification decreased USP1 expression and downregulation of USP1 ameliorated GC resistance of T-ALL through suppressing Aurora B expression and elevating GR level.