Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis.

OBJECTIVE: Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. METHODS: Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. RESULTS: Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. CONCLUSION: Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

Upcycling of polyethylene to gasoline through a self-supplied hydrogen strategy in a layered self-pillared zeolite.

Conversion of plastic wastes to valuable carbon resources without using noble metal catalysts or external hydrogen remains a challenging task. Here we report a layered self-pillared zeolite that enables the conversion of polyethylene to gasoline with a remarkable selectivity of 99% and yields of >80% in 4 h at 240 °C. The liquid product is primarily composed of branched alkanes (selectivity of 72%), affording a high research octane number of 88.0 that is comparable to commercial gasoline (86.6). In situ inelastic neutron scattering, small-angle neutron scattering, solid-state nuclear magnetic resonance, X-ray absorption spectroscopy and isotope-labelling experiments reveal that the activation of polyethylene is promoted by the open framework tri-coordinated Al sites of the zeolite, followed by ß-scission and isomerization on Brönsted acids sites, accompanied by hydride transfer over open framework tri-coordinated Al sites through a self-supplied hydrogen pathway to yield selectivity to branched alkanes. This study shows the potential of layered zeolite materials in enabling the upcycling of plastic wastes.

Handedness-Inverted and Stimuli-Responsive Circularly Polarized Luminescent Nano/Micromaterials Through Pathway-Dependent Chiral Supramolecular Polymorphism.

The precise manipulation of supramolecular polymorphs has been widely applied to control the morphologies and functions of self-assemblies, but is rarely utilized for the fabrication of circularly polarized luminescence (CPL) materials with tailored properties. Here, this work reports that an amphiphilic naphthalene-histidine compound (NIHis) readily self-assembled into distinct chiral nanostructures through pathway-dependent supramolecular polymorphism, which shows opposite and multistimuli responsive CPL signals. Specifically, NIHis display assembly-induced CPL from the polymorphic keto tautomer, which become predominant during enol-keto tautomerization shifting controlled by a bulk solvent effect. Interestingly, chiral polymorphs of nanofiber and microbelt with inverted CPL signals can be prepared from the same NIHis monomer in exactly the same solvent compositions and concentrations by only changing the temperature. The tunable CPL performance of the solid microbelts is realized under multi external physical or chemical stimuli including grinding, acid fuming, and heating. In particular, an emission color and CPL on-off switch based on the microbelt polymorph by reversible heating-cooling protocol is developed. This work brings a new approach for developing smart CPL materials via supramolecular polymorphism engineering.

Peiella sedimenti gen. nov., sp. nov., a novel taxon within the family Caulobacteraceae isolated from sediment of a river.

A Gram-stain-negative bacterium, designated XZ-24T, was isolated from sediment of a river in Mianyang city, Sichuan province, PR China. Cells (1.0-2.0 µm long and 0.4-0.5 µm in width) were strictly aerobic, non-spore-forming, rod shaped, prosthecate and motile by means of a polar flagellum. Growth occurred at 10-37 °C (optimum, 30 °C), at pH 5.0-9.0 (optimum pH 7.0) and with 0-3.0 % (w/v) NaCl (optimum 1.0 % NaCl). The results of phylogenetic analysis based on genomes and 16S rRNA gene sequences indicated that XZ-24T formed a distinct phyletic branch within the family Caulobacteraceae and was most closely related to members of the genera Brevundimonas, Caulobacter and Phenylobacterium with 95.3-96.5 % 16S rRNA gene sequence similarities. The average amino acid identities (AAI) between XZ-24T and species of the family Caulobacteraceae were 47.0-64.5 %, which were below the genus boundary (70 %). The predominant cellular fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0, C18 : 1ω7c 11-methyl and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), the isoprenoid quinone was Q-10, and the major polar lipids were 1,2-di-O-acyl-3-O-α-d-glucopyranuronosyl glycerol; 1,2-di-O-acyl-3-O-[d-glucopyranosyl-(1→4)-α-d glucopyranuronosyl] glycerol and phosphatidylglycerol. The genome size of XZ-24T was 2.64 Mb with a DNA G+C content of 68.9 %. On the basis of the evidence presented in this study, strain XZ-24T represents a novel species of a novel genus in the family Caulobacteraceae, for which the name Peiella sedimenti gen. nov., sp. nov. (Type strain XZ-24T=CCTCC AB 20 23 094T=KCTC 8038T) is proposed.

Degradation of Atrazine by an Anaerobic Microbial Consortium Enriched from Soil of an Herbicide-Manufacturing Plant.

Atrazine is an important herbicide that has been widely used for weed control in recent decades. However, with the extensive use of atrazine, its residue seriously pollutes the environment. Therefore, the microbial degradation and detoxification of atrazine have received extensive attention. To date, the aerobic degradation pathway of atrazine has been well studied; however, little is known about its anaerobic degradation in the environment. In this study, an anaerobic microbial consortium capable of efficiently degrading atrazine was enriched from soil collected from an herbicide-manufacturing plant. Six metabolites including hydroxyatrazine, deethylatrazine, N-isopropylammelide, deisopropylatrazine, cyanuric acid, and the novel metabolite 4-ethylamino-6-isopropylamino-1,3,5-triazine (EIPAT) were identified, and two putative anaerobic degradation pathways of atrazine were proposed: a hydrolytic dechlorination pathway is similar to that seen in aerobic degradation, and a novel pathway initiated by reductive dechlorination. During enrichment, Denitratisoma, Thiobacillus, Rhodocyclaceae_unclassified, Azospirillum, and Anaerolinea abundances significantly increased, dominating the enriched consortium, indicating that they may be involved in atrazine degradation. These findings provide valuable evidence for elucidating the anaerobic catabolism of atrazine and facilitating anaerobic remediation of residual atrazine pollution.

HNRNPC Regulates GLUT1/LDHA Pathway by Stabilizing FOXM1 mRNA to Promote the Progression and Aerobic Glycolysis of Multiple Myeloma.

OBJECTIVE: Multiple Myeloma (MM) is a malignant hematological disease. Heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) acts as an oncogene in a variety of cancers. However, the role of HNRNPC in MM has not been reported so far. METHODS: The mRNA and protein expressions of HNRN-PC and FOXM1 were detected by qRT-PCR and western blot. CCK8, EDU staining, flow cytometry and western blot were used to detect cell viability and cell cycle. The extracellular flux analyzer XF96 was used to detect the production of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Lactic acid and glucose levels in culture medium were detected by lactic acid assay kits and glucose assay kits, respectively. Then, the binding ability of HNRNPC with FOXM1 was detected by RIP and the stability of FOXM1 mRNA was appraised with qRT-PCR. With the application of qRT-PCR and western blot, the transfection efficacy of si-HNRNPC and Oe-FOXM1 was examined. Western blot was applied for the estimation of GLUT1/LDHA signaling pathway-related proteins. RESULTS: The expression of HNRNPC in MM cell line was abnormally elevated. HNRNPC silence significantly inhibited the proliferation, facilitated the apoptosis, induced cycle arrest, and suppressed aerobic glycolysis in MM cells, which were all reversed by FOXM1 overexpression. It was also found that the regulatory effect of HNRNPC is realized by stabilizing FOXM1 mRNA and regulating GLUT1/LDHA pathway. CONCLUSION: HNRNPC regulated GLUT1/LDHA pathway by stabilizing FOXM1 mRNA to promote the progression and aerobic glycolysis of MM.

Anaerobic Degradation of Dicamba via a Novel Catabolic Pathway by a Consortium Enriched from Deep Paddy Soil.

Dicamba is widely used in the paddy field to control broadleaf weeds. Dicamba easily migrates to deep soil, which is anoxic; however, the anaerobic catabolism of dicamba in paddy soil is still unknown. In this study, an anaerobic dicamba-degrading consortium was enriched from deep paddy soil. The consortium completely degraded 0.83 mM dicamba within 7 days. Five metabolites were identified, one of which is a new metabolite, 2,5-dichlorophenol, and a novel anaerobic dicamba degradation pathway was proposed. 2.5 mM dicamba, 1.5-2.0% NaCl, and 20 mM electron acceptors Na2SO4, NaNO3, and FeCl3, and 0.5 mM or more of metabolites 3-CP and 2,5-DCP strongly inhibited the degradation efficiency. During enrichment, the microbial community of the consortium was significantly changed with OTU numbers, and diversity decreased. The study is valuable to elucidate the catabolism and ecotoxicology studies of dicamba in paddy soil and to facilitate the engineering application of anaerobic technology to treat dicamba-manufacturing wastewater.

Down-regulation of Musashi-2 exerts antileukemic effects on acute lymphoblastic leukemia cells and increases sensitivity to dexamethasone.

Musashi-2 (MSI2), implicated in the oncogenesis and propagation of a broad array of malignancies, inclusive of certain leukemia, remains a nascent field of study within the context of acute lymphoblastic leukemia (ALL). Using lentiviral transfection, ALL cells with stable MSI2 knockdown were engineered. A suite of analytic techniques - a CCK-8 assay, flow cytometry, qRT-PCR, and western blotting - were employed to evaluate cellular proliferation, cell cycle arrest, and apoptosis and to confirm differential gene expression. The suppression of MSI2 expression yielded significant results: inhibition of cell proliferation, G0/G1 cell cycle arrest, and induced apoptosis in ALL cell lines. Furthermore, it was noted that MSI2 inhibition heightened the responsiveness of ALL cells to dexamethasone. Significantly, the depletion of MSI2 prompted the translocation of GR from the cytoplasm to the nucleus upon dexamethasone treatment, consequently leading to enhanced sensitivity. Additionally, the FOXO1/4 signaling pathway contributed to the biological effects of ALL cells evoked by MSI2 silencing. Our study offers novel insight into the inhibitory effects of MSI2 suppression on ALL cells, positing MSI2 as a promising therapeutic target in the treatment of ALL.

Flavobacterium sedimenticola sp. nov., isolated from sediment.

A novel yellow-pigmented bacterial strain, designated YZ-48T, was isolated from the sediment of the Yangtze River, PR China. Cells were Gram-stain-negative, non-motile, rod-shaped, strictly aerobic, catalase-positive and oxidase-positive. The strain grew optimally on R2A medium at 37 °C, pH 7.0 and with 1.0 % (w/v) NaCl. Strain YZ-48T showed the closest 16S rRNA gene sequence similarity to Flavobacterium solisilvae SE-s27T (96.4 %) and F. dankookense DSM 25687T (96.2 %). The phylogenetic trees based on 16S rRNA gene sequences showed that strain YZ-48T belonged to the genus Flavobacterium but formed a distinct phylogenetic lineage. The obtained average nucleotide identity and digital DNA-DNA hybridization values between YZ-48T and the two closest strains were 75.0 and 74.5 % and 19.6 and 19.0 %, respectively. The sole respiratory quinone was MK-6. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and three unidentified polar lipids. The major cellular fatty acids were iso-C16 : 0, iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and iso-C16 : 0 3-OH. The DNA G+C content was 40.2 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain YZ-48T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium sedimenticola sp. nov. is proposed, with strain YZ-48T (=KCTC 82329T=CCTC AB 2023061T=MCCC 1K08804T) as the type strain.

Safety and efficacy of remimazolam tosilate combined with low-dose fentanyl for procedural sedation in obese patients undergoing gastroscopy: study protocol for a single-centre, double-blind, randomised controlled trial.

INTRODUCTION: Obese patients are susceptible to hypoxaemia during procedural sedation. Propofol combined with low-dose opioids is commonly used as a sedation strategy, but it can exacerbate hypoxaemia by causing cardiopulmonary depression and airway obstruction, especially in obese patients. Remimazolam, a novel ultra-short-acting benzodiazepine, has minimal accumulative effects and less cardiorespiratory depression. This study aims to evaluate the safety and efficacy of combining remimazolam tosilate with low-dose fentanyl as an alternative option for procedural sedation in obese patients undergoing gastroscopy. METHODS AND ANALYSIS: This randomised controlled trial (RCT) will be conducted in the Endoscopy Centre of the First Affiliated Hospital of Xiamen University, recruiting 174 participants scheduled for painless gastroscopy with a body mass index of 30-39.9 kg×m-2. All patients will be randomly divided into two groups in a 1:1 ratio. The sedation strategy of the intervention group is remimazolam tosilate combined with fentanyl, while the control group is propofol combined with fentanyl. The primary outcome is the incidence of hypoxaemia and the secondary outcomes include the time to ambulation, need for airway manoeuvres and rescue sedation, sleep quality, the incidence of sedation failure, adverse events and the cost of sedatives. All statistical tests will be performed using IBM SPSS V.20.0 statistical software. A p value<0.05 is considered statistically significant. ETHICS AND DISSEMINATION: This RCT was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Xiamen University (Scientific Research Ethics Review 2022, No.093). The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2200067076.

Vibrio chanodichtyis sp. nov., isolated from the intestine of swordfish Chanodichthys dabryi.

A Gram-stain-negative, facultatively anaerobic, motile, curved-rod-shaped flagellated bacterium, designated DSL-7T, was isolated from the intestine of Chanodichthys dabryi in the Yangtze river, PR China. The strain grew optimally in tryptone soy broth medium at 37 °C, pH 7.0 and with 1 % (w/v) NaCl. Strain DSL-7T showed less than 96.2 % 16S rRNA gene sequence similarity to type strains of the genus Vibrio. Phylogenetic analysis based on genomes indicated that strain DSL-7T belonged to the genus Vibrio and formed a subclade with Vibrio mimicus NCTC 11435T, Vibrio metoecus OP3HT, Vibrio cholerae ATCC 14035T, Vibrio albensis ATCC14547T, Vibrio paracholerae OP3HEDC-792T and Vibrio tarriae 2521-89T. The average nucleotide identity (ANI) and in digital DNA-DNA hybridization (dDDH) values between DSL-7T and closely related type strains were below the accepted threshold to delineate a new species of 95 and 70 %, respectively. The major cellular fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 0, summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and C14 : 0. The genomic DNA G+C content was 47.6 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain DSL-7T represents a novel species of the genus Vibrio, for which the name Vibrio chanodichtyis sp. nov. is proposed, with strain DSL-7T (=KCTC 92851T=CCTCC AB 2022396T) as the type strain.

Jeotgalibaca caeni sp. nov., isolated from biochemical tank sludge.

A Gram-stain-positive, coccoid-shaped, non-spore-forming, facultatively anaerobic bacterium, designated YN-L-12T, was isolated from the activate sludge of a pesticide plant. Colonies on tryptone soya agar were small, white, opaque and circular. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain YN-L-12T belonged to the genus of Jeotgalibaca, and showed the highest similarity to Jeotgalibaca arthritidis 1805-02T (97.0 %), followed by Jeotgalibaca ciconiae H21T32T (96.5 %), Jeotgalibaca porci 1804-02T (95.6 %) and Jeotgalibaca dankookensis EX-07T (95.4 %). The strain grew at 15-37 °C (optimum, 30 °C), with 0-6.5 % (w/v) NaCl (optimum, 0.5 %) and at pH 7-9 (optimum, pH 7.5). The major fatty acids were C18 : 1 ω9c, C16 : 1 ω9c and C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, glycolipid and an unidentified lipid. The DNA G+C content of the strain was 41.1 mol%. Average nucleotide identity values between strain YN-L-12T and J. arthritidis 1805-02T and J. ciconiae H21T32T were 72.8 and 72.3 %, respectively. The digital DNA-DNA hybridization values between YN-L-12T and J. arthritidis 1805-02T and J. ciconiae H21T32T were 24.1 and 20.3 %, respectively. According to the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain YN-L-12T represents a novel species of the genus Jeotgalibaca, for which the name Jeotgalibaca caeni sp. nov. is proposed, with strain YN-L-12T (=KCTC 43533T=CCTCC AB 2022400T) as the type strain.

Cascade signal amplification strategy by coupling chemical redox-cycling and Fenton-like reaction: Toward an ultrasensitive split-type fluorescent immunoassay.

An ultrasensitive split-type fluorescent immunobiosensor has been reported based on a cascade signal amplification strategy by coupling chemical redox-cycling and Fenton-like reaction. In this strategy, Cu2+ could oxidize chemically o-phenylenediamine (OPD) to generate photosensitive 2, 3-diaminophenazine (DAP) and Cu+/Cu0. On one hand, the generated Cu0 in turn catalyzed the oxidation of OPD. On the other hand, the introduced H2O2 reacted with Cu + ion to produce hydroxyl radicals (·OH) and Cu2+ ion through a Cu + -mediated Fenton-like reaction. The produced ·OH and recycled Cu2+ ion could take turns oxidizing OPD to generate more photoactive DAP, which triggering a self-sustaining chemical redox-cycling reaction and leading to a remarkable fluorescent improvement. It was worth mentioning that the cascade reaction did not stop until OPD molecules were completely consumed. Based on the H2O2-triggered cascade signal amplification, the strategy was exploited for the construction of split-type fluorescent immunoassay by taking interleukin-6 (IL-6) as the model target. It was realized for the ultrasensitive determination of IL-6 in a linear ranging from 20 fg/mL to 10 pg/mL with a limit of detection of 5 fg/mL. The study validated the practicability of the cascade signal amplification on the fluorescent bioanalysis and the superior performance in fluorescent immunoassay. It is expected that the strategy would offer new opportunities to develop ultrasensitive fluorescent methods for biosensor and bioanalysis.

A Sensitive Fluorescence Sensor for Tetracycline Determination Based on Adenine Thymine-Rich Single-Stranded DNA-Templated Copper Nanoclusters.

A sensitive fluorescent sensor has been developed for the determination of tetracycline (TC) using adenine thymine (AT)-rich single-stranded DNA (ssDNA) templated copper nanoclusters (CuNCs) as a fluorescent probe. Fluorescent ssDNA-CuNCs were synthesized by employing AT-rich ssDNA as templates and ascorbic acid as reducing agents through a facile one-step method. The as-prepared ssDNA-CuNCs exhibited strong fluorescence with a large Stokes shift (240 nm) and stable fluorescence emission. In the presence of TC, the fluorescent intensity of ssDNA-CuNCs was obviously decreased through the inner filter effect, due to the spectral overlapping between ssDNA-CuNCs and TC. Under the optimal conditions, the strategy exhibited sensitive detection of TC with a linear range from 2 nM to 30 µM and with a limit of detection of 0.5 nM. Furthermore, the sensor was successfully applied for the detection of TC in milk samples. Therefore, it provided a simple, rapid, and label-free fluorescent method for TC detection.

Low-temperature electrolytes based on linear carboxylic ester co-solvents for SiO x /graphite composite anodes.

Silicon-based anode materials have been applied in lithium-ion batteries with high energy density. However, developing electrolytes that can meet the specific requirements of these batteries at low temperatures still remains a challenge. Herein, we report the effect of linear carboxylic ester ethyl propionate (EP), as the co-solvent in a carbonate-based electrolyte, on SiO x /graphite (SiOC) composite anodes. Using electrolytes with EP, the anode provides better electrochemical performance at both low temperatures and ambient temperature, showing a capacity of 680.31 mA h g-1 at -50 °C and 0.1C (63.66% retention relative to that at 25 °C), and a capacity retention of 97.02% after 100 cycles at 25 °C and 0.5C. Within the EP-containing electrolyte, SiOC‖LiCoO2 full cells also exhibit superior cycling stability at -20 °C for 200 cycles. These substantial improvements of the EP co-solvent at low temperatures are probably due to its involvement to form a solid electrolyte interphase with high integrity and facile transport kinetics in electrochemical processes.

Sustained anaerobic degradation of 4-chloro-2-methylphenoxyacetic acid by acclimated sludge in a continuous-flow reactor.

4-Chloro-2-methylphenoxyacetic acid (MCPA) is a widely used herbicide across the world. MCPA is persistent and easily transports into anoxic environment, such as groundwater, sediments and deep soils. However, little research on anaerobic microbial degradation of MCPA was carried out. The functional microorganisms as well as the catabolic pathway are still unknown. In this research, an anaerobic MCPA-degrading bacterial consortium was enriched from the river sediment near a pesticide-manufacturing plant. After about 6 months' acclimation, the MCPA transformation rate of the consortium reached 4.32 µmol g-1 day-1, 25 times faster than that of the original sludge. 96% of added MCPA (2.5 mM) was degraded within 9 d of incubation. Three metabolites including 4-chloro-2-methylphenol (MCP), 2-methylphenol (2-MP) and phenol were identified during the anaerobic degradation of MCPA. An anaerobic catabolic pathway was firstly proposed: firstly, MCPA was transformed to MCP via the cleavage of the aryl ether, then MCP was reductively dechlorinated to 2-MP which was further demethylated to phenol. The 16S rRNA gene amplicon sequencing revealed a substantial shift in the bacterial community composition after the acclimation. SBR1031, Acidaminococcaceae, Aminicenantales, Syntrophorhabdus, Acidaminobacter, Bacteroidetes_vadinHA17, Methanosaeta, Bathyarchaeia, KD4-96, Anaeromyxobacter, and Dehalobacter were significantly increased in the enriched consortium after acclimation, and positively correlated with the anaerobic degradation of MCPA as suggested by heat map correlation analysis. This study provides a basis for further elucidation of the anaerobic catabolism of MCPA, and contributes to developing efficient and low-cost anaerobic treatment technologies for MCPA pollution.

Amantadine Toxicity in Apostichopus japonicus Revealed by Proteomics.

Amantadine exposure can alter biological processes in sea cucumbers, which are an economically important seafood in China. In this study, amantadine toxicity in Apostichopus japonicus was analyzed by oxidative stress and histopathological methods. Quantitative tandem mass tag labeling was used to examine changes in protein contents and metabolic pathways in A. japonicus intestinal tissues after exposure to 100 µg/L amantadine for 96 h. Catalase activity significantly increased from days 1 to 3 of exposure, but it decreased on day 4. Superoxide dismutase and glutathione activities were inhibited throughout the exposure period. Malondialdehyde contents increased on days 1 and 4 but decreased on days 2 and 3. Proteomics analysis revealed 111 differentially expressed proteins in the intestines of A. japonicus after amantadine exposure compared with the control group. An analysis of the involved metabolic pathways showed that the glycolytic and glycogenic pathways may have increased energy production and conversion in A. japonicus after amantadine exposure. The NF-κB, TNF, and IL-17 pathways were likely induced by amantadine exposure, thereby activating NF-κB and triggering intestinal inflammation and apoptosis. Amino acid metabolism analysis showed that the leucine and isoleucine degradation pathways and the phenylalanine metabolic pathway inhibited protein synthesis and growth in A. japonicus. This study investigated the regulatory response mechanisms in A. japonicus intestinal tissues after exposure to amantadine, providing a theoretical basis for further research on amantadine toxicity.

Decreased transthyretin predicts a poor prognosis in primary myelodysplastic syndrome.

Background: This study aims to investigate the prognostic significance of transthyretin in newly diagnosed myelodysplastic syndromes (MDS). Methods: The clinical, laboratory, and follow-up data of 280 newly diagnosed patients with MDS were collected. The relationship between serum transthyretin levels and overall survival (OS) and leukemia-free survival (LFS) were analyzed by Kaplan-Meier analysis and Cox Regression Model. Result: In the MDS cohort, there were 121 cases in the low transthyretin group and 159 cases in the normal transthyretin group. MDS patients with decreased transthyretin had a higher risk score on the Revised International Prognostic Scoring System (IPSS-R) (p = 0.004) and on the molecular IPSS (IPSS-M) (p = 0.005), a higher frequency of TP53 mutation (p < 0.0001), a shorter OS (p < 0.0001) and LFS (p < 0.0001). Multivariate analyses showed that higher IPSS-R and IPSS-M score were adverse factors for OS (p = 0.008 and p = 0.015, respectively) and LFS (p = 0.024 and p = 0.005, respectively). Mutations of TP53 and NRAS were also poor factors for LFS (p = 0.034 and p = 0.018, respectively). Notably, decreased transthyretin was an independent adverse predictor for OS (p = 0.009, HR = 0.097, 95%CI, 0.017-0.561) but not for LFS (p = 0.167) when IPSS-R was included in the Cox regression model and an independent poor one for OS (p = 0.033, HR = 0.267, 95%CI, 0.080-0.898) and LFS (p = 0.024, HR = 0.290, 95%CI, 0.099-0.848) while IPSS-M involved. Conclusion: The results indicate that decreased transthyretin could be an independent adverse prognostic factor in patients with MDS and may provide a supplement to IPSS-R and IPSS-M.

Determination of trypsin using protamine mediated fluorescent enhancement of DNA templated Au nanoclusters.

A fluorescent method is described for trypsin determination through the strong electrostatic interactions between cationic polyelectrolytes and single-stranded DNA (ssDNA) templated Au nanoclusters (AuNCs). The ssDNA-AuNCs display improved fluorescence emission with excitation/emission maxima at 280/475 nm after being incorporated with poly(diallyldimethylammonium chloride) (PDDA). Fluorescent enhancement is mainly attributed to the electrostatic interactions occurring  between PDDA and ssDNA templates. This can make the conformation of the ssDNA templates to change. Thus, it offers a better microenvironment for stabilizing and protecting ssDNA-AuNCs, and results in fluorescence emission enhancement. By using protamine as a model, the method is employed for the determination of trypsin. The assay enables trypsin to be determined with good sensitivity and a linear response ranging from 5 ng⋅mL-1 to 60 ng⋅mL-1 with a 1.5 ng⋅mL-1 limit of detection. It is also extended to determine  the trypsin contents in human's serum samples with recoveries between 98.7% and 103.5% with relative standard deviations (RSDs) between 3.5% and 4.8%. A novel fluorescent strategy has been developed for of trypsin determination by using protamine mediated fluorescent enhancement of DNA templated Au nanoclusters.