ABSTRACT
Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD41-4. Although high-resolution structures of Env in a complex with the soluble domains of CD4 have been determined, the binding process is less understood in native membranes5-13. Here we used cryo-electron tomography to monitor Env-CD4 interactions at the membrane-membrane interfaces formed between HIV-1 and CD4-presenting virus-like particles. Env-CD4 complexes organized into clusters and rings, bringing the opposing membranes closer together. Env-CD4 clustering was dependent on capsid maturation. Subtomogram averaging and classification revealed that Env bound to one, two and finally three CD4 molecules, after which Env adopted an open state. Our data indicate that asymmetric HIV-1 Env trimers bound to one and two CD4 molecules are detectable intermediates during virus binding to host cell membranes, which probably has consequences for antibody-mediated immune responses and vaccine immunogen design.
Subject(s)
CD4 Antigens , Cell Membrane , HIV Envelope Protein gp120 , HIV-1 , Protein Multimerization , Humans , AIDS Vaccines/chemistry , AIDS Vaccines/immunology , Capsid/chemistry , Capsid/metabolism , Capsid/ultrastructure , CD4 Antigens/chemistry , CD4 Antigens/metabolism , CD4 Antigens/ultrastructure , Cell Membrane/chemistry , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Cryoelectron Microscopy , Electron Microscope Tomography , HIV Antibodies/immunology , HIV Envelope Protein gp120/chemistry , HIV Envelope Protein gp120/metabolism , HIV Envelope Protein gp120/ultrastructure , HIV Infections/virology , HIV-1/chemistry , HIV-1/ultrastructure , Virion/chemistry , Virion/metabolism , Virion/ultrastructureABSTRACT
Clarifying the reaction pathways at the solid-water interface and in bulk water solution is of great significance for the design of heterogeneous catalysts for selective oxidation of organic pollutants. However, achieving this goal is daunting because of the intricate interfacial reactions at the catalyst surface. Herein, we unravel the origin of the organic oxidation reactions with metal oxide catalysts, revealing that the radical-based advanced oxidation processes (AOPs) prevail in bulk water but not on the solid catalyst surfaces. We show that such differing reaction pathways widely exist in various chemical oxidation (e.g., high-valent Mn3+ and MnOX) and Fenton and Fenton-like catalytic oxidation (e.g., Fe2+ and FeOCl catalyzing H2O2, Co2+ and Co3O4 catalyzing persulfate) systems. Compared with the radical-based degradation and polymerization pathways of one-electron indirect AOP in homogeneous reactions, the heterogeneous catalysts provide unique surface properties to trigger surface-dependent coupling and polymerization pathways of a two-electron direct oxidative transfer process. These findings provide a fundamental understanding of catalytic organic oxidation processes at the solid-water interface, which could guide the design of heterogeneous nanocatalysts.
ABSTRACT
A precise modulation of heterogeneous catalysts in structural and surface properties promises the development of more sustainable advanced oxidation water purification technologies. However, while catalysts with superior decontamination activity and selectivity are already achievable, maintaining a long-term service life of such materials remains challenging. Here, we propose a crystallinity engineering strategy to break the activity-stability tradeoff of metal oxides in Fenton-like catalysis. The amorphous/crystalline cobalt-manganese spinel oxide (A/C-CoMnOx) provided highly active, hydroxyl group-rich surface, with moderate peroxymonosulfate (PMS)-binding affinity and charge transfer energy and strong pollutant adsorption, to trigger concerted radical and nonradical reactions for efficient pollutant mineralization, thereby alleviating the catalyst passivation by oxidation intermediate accumulation. Meanwhile, the surface-confined reactions, benefited from the enhanced adsorption of pollutants at A/C interface, rendered the A/C-CoMnOx/PMS system ultrahigh PMS utilization efficiency (82.2%) and unprecedented decontamination activity (rate constant of 1.48 min-1) surpassing almost all the state-of-the-art heterogeneous Fenton-like catalysts. The superior cyclic stability and environmental robustness of the system for real water treatment was also demonstrated. Our work unveils a critical role of material crystallinity in modulating the Fenton-like catalytic activity and pathways of metal oxides, which fundamentally improves our understanding of the structure-activity-selectivity relationships of heterogeneous catalysts and may inspire material design for more sustainable water purification application and beyond.
ABSTRACT
Nonradical Fenton-like catalysis offers opportunities to overcome the low efficiency and secondary pollution limitations of existing advanced oxidation decontamination technologies, but realizing this on transition metal spinel oxide catalysts remains challenging due to insufficient understanding of their catalytic mechanisms. Here, we explore the origins of catalytic selectivity of Fe-Mn spinel oxide and identify electron delocalization of the surface metal active site as the key driver of its nonradical catalysis. Through fine-tuning the crystal geometry to trigger Fe-Mn superexchange interaction at the spinel octahedra, ZnFeMnO4 with high-degree electron delocalization of the Mn-O unit was created to enable near 100% nonradical activation of peroxymonosulfate (PMS) at unprecedented utilization efficiency. The resulting surface-bound PMS* complex can efficiently oxidize electron-rich pollutants with extraordinary degradation activity, selectivity, and good environmental robustness to favor water decontamination applications. Our work provides a molecule-level understanding of the catalytic selectivity and bimetallic interactions of Fe-Mn spinel oxides, which may guide the design of low-cost spinel oxides for more selective and efficient decontamination applications.
Subject(s)
Electrons , Oxides , Catalysis , Magnesium Oxide/chemistry , Oxides/chemistry , Peroxides/chemistryABSTRACT
Shewanella oneidensis MR-1 has found widespread applications in pollutant transformation and bioenergy production, closely tied to its outstanding heme synthesis capabilities. However, this significant biosynthetic potential is still unexploited so far. Here, we turned this bacterium into a highly-efficient bio-factory for green synthesis of 5-Aminolevulinic Acid (5-ALA), an important chemical for broad applications in agriculture, medicine, and the food industries. The native C5 pathway genes of S. oneidensis was employed, together with the introduction of foreign anti-oxidation module, to establish the 5-ALA production module, resulting 87-fold higher 5-ALA yield and drastically enhanced tolerance than the wild type. Furthermore, the metabolic flux was regulated by using CRISPR interference and base editing techniques to suppress the competitive pathways to further improve the 5-ALA titer. The engineered strain exhibited 123-fold higher 5-ALA production capability than the wild type. This study not only provides an appealing new route for 5-ALA biosynthesis, but also presents a multi-dimensional modularized engineering strategy to broaden the application scope of S. oneidensis.
Subject(s)
Aminolevulinic Acid , Metabolic Engineering , Shewanella , Shewanella/genetics , Shewanella/metabolism , Aminolevulinic Acid/metabolismABSTRACT
Bacteria capable of direct ammonia oxidation (Dirammox) play important roles in global nitrogen cycling and nutrient removal from wastewater. Dirammox process, NH3 â NH2 OH â N2 , first defined in Alcaligenes ammonioxydans HO-1 and encoded by dnf gene cluster, has been found to widely exist in aquatic environments. However, because of multidrug resistance in Alcaligenes species, the key genes involved in the Dirammox pathway and the interaction between Dirammox process and the physiological state of Alcaligenes species remain unclear. In this work, ammonia removal via the redistribution of nitrogen between Dirammox and microbial growth in A. ammonioxydans HO-1, a model organism of Alcaligenes species, was investigated. The dnfA, dnfB, dnfC, and dnfR genes were found to play important roles in the Dirammox process in A. ammonioxydans HO-1, while dnfH, dnfG, and dnfD were not essential genes. Furthermore, an unexpected redistribution phenomenon for nitrogen between Dirammox and cell growth for ammonia removal in HO-1 was revealed. After the disruption of the Dirammox in HO-1, more consumed NH4 + was recovered as biomass-N via rapid metabolic response and upregulated expression of genes associated with ammonia transport and assimilation, tricarboxylic acid cycle, sulfur metabolism, ribosome synthesis, and other molecular functions. These findings deepen our understanding of the molecular mechanisms for Dirammox process in the genus Alcaligenes and provide useful information about the application of Alcaligenes species for ammonia-rich wastewater treatment.
Subject(s)
Ammonium Compounds , Ammonium Compounds/metabolism , Alcaligenes/genetics , Alcaligenes/metabolism , Ammonia/toxicity , Ammonia/metabolism , Wastewater , Nitrogen/metabolism , Denitrification , Oxidation-Reduction , BioreactorsABSTRACT
The voltage-dependent anion channel 2 (VDAC2) is the abundant protein in the outer mitochondrial membrane. Opening VDAC2 pores leads to the induction of mitochondrial energy and material transport, facilitating interaction with various mitochondrial proteins implicated in essential processes such as cell apoptosis and proliferation. To investigate the VDAC2 in lower vertebrates, we identified Lr-VDAC2, a homologue of VDAC2 found in lamprey (Lethenteron reissneri), sharing a sequence identity of greater than 50 % with its counterparts. Phylogenetic analysis revealed that the position of Lr-VDAC2 aligns with the lamprey phylogeny, indicating its evolutionary relationship within the species. The Lr-VDAC2 protein was primarily located in the mitochondria of lamprey cells. The expression of the Lr-VDAC2 protein was elevated in high energy-demanding tissues, such as the gills, muscles, and myocardial tissue in normal lampreys. Lr-VDAC2 suppressed H2O2 (hydrogen peroxide)-induced 293 T cell apoptosis by reducing the expression levels of Caspase 3, Caspase 9, and Cyt C (cytochrome c). Further research into the mechanism indicated that the Lr-VDAC2 protein inhibited the pro-apoptotic activity of BAK (Bcl-2 antagonist/killer) protein by downregulating its expression at the protein translational level, thus exerting an anti-apoptotic function similar to the role of VDAC2 in humans.
Subject(s)
Apoptosis , Fish Proteins , Lampreys , Voltage-Dependent Anion Channel 2 , Animals , Humans , Amino Acid Sequence , bcl-2 Homologous Antagonist-Killer Protein/metabolism , Down-Regulation/drug effects , Fish Proteins/genetics , Fish Proteins/immunology , Gene Expression Profiling/veterinary , Gene Expression Regulation , HEK293 Cells , Hydrogen Peroxide , Lampreys/genetics , Lampreys/immunology , Phylogeny , Sequence Alignment/veterinary , Voltage-Dependent Anion Channel 2/metabolismABSTRACT
The environmental dissemination of extracellular antibiotic resistance genes (eARGs) in wastewater and natural water bodies has aroused growing ecological concerns. The coexisting chemical pollutants in water are known to markedly affect the eARGs transfer behaviors of the environmental microbial community, but the detailed interactions and specific impacts remain elusive so far. Here, we revealed a concentration-dependent impact of dimethyl phthalate (DMP) and several other types of phthalate esters (common water pollutants released from plastics) on the natural transformation of eARGs. The DMP exposure at an environmentally relevant concentration (10 µg/L) resulted in a 4.8-times raised transformation frequency of Acinetobacter baylyi but severely suppressed the transformation at a high concentration (1000 µg/L). The promotion by low-concentration DMP was attributed to multiple mechanisms, including increased bacterial mobility and membrane permeability to facilitate eARGs uptake and improved resistance of the DMP-bounded eARGs (via noncovalent interaction) to enzymatic degradation (with suppressed DNase activity). Similar promoting effects of DMP on the eARGs transformation were also found in real wastewater and biofilm systems. In contrast, higher-concentration DMP suppressed the eARGs transformation by disrupting the DNA structure. Our findings highlight a potentially underestimated eARGs spreading in aquatic environments due to the impacts of coexisting chemical pollutants and deepen our understanding of the risks of biological-chemical combined pollution in wastewater and environmental water bodies.
Subject(s)
Drug Resistance, Microbial , Phthalic Acids , Drug Resistance, Microbial/genetics , Wastewater , Biofilms/drug effects , Water Pollutants, Chemical/toxicityABSTRACT
Genomic integration techniques offer opportunities for generation of engineered microorganisms with improved or even entirely new functions but are currently limited by inability for efficient insertion of long genetic payloads due to multiplexing. Herein, using Shewanella oneidensis MR-1 as a model, we developed an optimized CRISPR-associated transposase from cyanobacteria Scytonema hofmanni (ShCAST system), which enables programmable, RNA-guided transposition of ultra-long DNA sequences (30 kb) onto bacterial chromosomes at â¼100% efficiency in a single orientation. In this system, a crRNA (CRISPR RNA) was used to target multicopy loci like insertion-sequence elements or combining I-SceI endonuclease, thereby allowing efficient single-step multiplexed or iterative DNA insertions. The engineered strain exhibited drastically improved substrate diversity and extracellular electron transfer ability, verifying the success of this system. Our work greatly expands the application range and flexibility of genetic engineering techniques and may be readily extended to other bacteria for better controlling various microbial processes.
Subject(s)
Clustered Regularly Interspaced Short Palindromic Repeats , Integrases , Base Sequence , CRISPR-Cas Systems/genetics , Genomics , Integrases/metabolism , RNAABSTRACT
Volatile organic compounds (VOCs) are a class of hazardous gases that are widely present in the atmosphere and cause great harm to human health. In this paper, a ratiometric fluorescent probe (Dye@Eu-MOFs) based on a dye-functionalized metal-organic framework was designed to detect VOCs, which showed high sensitivity and specificity for acetaldehyde solution and vapor. A linear correlation between the integrated fluorescence intensity (I510/I616) and the concentration of acetaldehyde was investigated, enabling a quantitative analysis of acetaldehyde in the ranges of 1 × 10-4~10-5 µL/mL, with a low detection limit of 8.12 × 10-4 mg/L. The selective recognition of acetaldehyde could be clearly distinguished by the naked eye under the excitation of UV light. The potential sensing mechanism was also discussed. Significantly, a molecular logic gate was constructed based on the whole system, and finally, a molecular logic network system for acetaldehyde detection connecting basic and integrated logic operations was realized. This strategy provided an effective guiding method for constructing a molecular-level logic gate for acetaldehyde detection on a simple platform.
ABSTRACT
RSK1, a downstream kinase of the MAPK pathway, has been shown to regulate multiple cellular processes and is essential for lytic replication of a variety of viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV). Besides phosphorylation, it is not known whether other post-translational modifications play an important role in regulating RSK1 function. We demonstrate that RSK1 undergoes robust SUMOylation during KSHV lytic replication at lysine residues K110, K335, and K421. SUMO modification does not alter RSK1 activation and kinase activity upon KSHV ORF45 co-expression, but affects RSK1 downstream substrate phosphorylation. Compared to wild-type RSK1, the overall phosphorylation level of RxRxxS*/T* motif is significantly declined in RSK1K110/335/421R expressing cells. Specifically, SUMOylation deficient RSK1 cannot efficiently phosphorylate eIF4B. Sequence analysis showed that eIF4B has one SUMO-interacting motif (SIM) between the amino acid position 166 and 170 (166IRVDV170), which mediates the association between eIF4B and RSK1 through SUMO-SIM interaction. These results indicate that SUMOylation regulates the phosphorylation of RSK1 downstream substrates, which is required for efficient KSHV lytic replication.
Subject(s)
Herpesvirus 8, Human/physiology , Host-Pathogen Interactions/physiology , Ribosomal Protein S6 Kinases, 90-kDa/metabolism , Sumoylation/physiology , Virus Replication/physiology , Cell Line , HumansABSTRACT
Prohibitin 2 (PHB2) is an evolutionarily conserved and functionally diverse protein that plays an important role in multiple cellular functions, including cell proliferation, cell migration, and apoptosis, and is also known to participate in the process of tumorigenesis and development. In this study, the lamprey PHB2 (Lm-PHB2) gene was over-expressed in KRAS (kirsten rat sarcoma viral oncogene homolog)-mutated non-small cell lung carcinoma (NSCLC) cells to investigate its effect on cell proliferation. The effects of Lm-PHB2 protein on the proliferation of NSCLC cells were determined by treating cells with the purified recombinant Lm-PHB2 protein (rLm-PHB2) followed by cell counting kit (CCK) assays and flow cytometry. Analysis showed that rLm-PHB2 blocked cells in the G2 phase and inhibited the cell proliferation of A549, Calu-1, and NCI-H226 to various degrees. The effect on Calu-1 cells was the most obvious and was concentration- and time-dependent. Similarly, cells transfected with the pEGFP-N1-Lm-PHB2 plasmid also resulted in the suppression of proliferation in A549 cells and Calu-1 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that Lm-PHB2 inhibited cell proliferation by repressing the transcription of PLK1 (polo-like kinase 1), Wee1 (wee1 kinase), CCNB1 (cyclin B1), and CDC25C (cell division control protein 25C). According to western blot analysis, Lm-PHB2 not only down-regulated the expression of PLK1, Wee1, CCNB1, and CDC25C but also reduced the phosphorylation levels of CCNB1 and CDC25C, thus blocking Calu-1 cells in G2/M phase. Our findings demonstrate a function of lamprey PHB2 that may inhibit the proliferation of some NSCLC cells by down-regulating the expression and phosphorylation of cell cycle-associated proteins.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Phosphorylation , Lampreys , Prohibitins , Cell Proliferation/physiology , Cell Cycle , Cell Line, Tumor , ApoptosisABSTRACT
Microbial extracellular electron transfer (EET) is the basis for many microbial processes involved in element geochemical recycling, bioenergy harvesting, and bioremediation, including the technique for remediating U(VI)-contaminated environments. However, the low EET rate hinders its full potential from being fulfilled. The main challenge for engineering microbial EET is the difficulty in optimizing cell resource allocation for EET investment and basic metabolism and the optimal coordination of the different EET pathways. Here, we report a novel combinatorial optimization strategy with a physiologically adapted regulatory platform. Through exploring the physiologically adapted regulatory elements, a 271.97-fold strength range, autonomous, and dynamic regulatory platform was established for Shewanella oneidensis, a prominent electrochemically active bacterium. Both direct and mediated EET pathways are modularly reconfigured and tuned at various intensities with the regulatory platform, which were further assembled combinatorically. The optimal combinations exhibit up to 16.12-, 4.51-, and 8.40-fold improvements over the control in the maximum current density (1009.2 mA/m2) of microbial electrolysis cells and the voltage output (413.8 mV) and power density (229.1 mW/m2) of microbial fuel cells. In addition, the optimal strains exhibited up to 6.53-fold improvement in the radionuclide U(VI) removal efficiency. This work provides an effective and feasible approach to boost microbial EET performance for environmental applications.
Subject(s)
Bioelectric Energy Sources , Shewanella , Electrons , Electron Transport , Biodegradation, Environmental , Shewanella/metabolismABSTRACT
Plastics-microorganism interactions have aroused growing environmental and ecological concerns. However, previous studies concentrated mainly on the direct interactions and paid little attention to the ecotoxicology effects of phthalates (PAEs), a common plastic additive that is continuously released and accumulates in the environment. Here, we provide insights into the impacts of PAEs on the dissemination of antibiotic resistance genes (ARGs) among environmental microorganisms. Dimethyl phthalate (DMP, a model PAE) at environmentally relevant concentrations (2-50 µg/L) significantly boosted the plasmid-mediated conjugation transfer of ARGs among intrageneric, intergeneric, and wastewater microbiota by up to 3.82, 4.96, and 4.77 times, respectively. The experimental and molecular dynamics simulation results unveil a strong interaction between the DMP molecules and phosphatidylcholine bilayer of the cell membrane, which lowers the membrane lipid fluidity and increases the membrane permeability to favor transfer of ARGs. In addition, the increased reactive oxygen species generation and conjugation-associated gene overexpression under DMP stress also contribute to the increased gene transfer. This study provides fundamental knowledge of the PAE-bacteria interactions to broaden our understanding of the environmental and ecological risks of plastics, especially in niches with colonized microbes, and to guide the control of ARG environmental spreading.
Subject(s)
Anti-Bacterial Agents , Bacteria , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Bacteria/genetics , Genes, Bacterial , Plastics , Gene Transfer, HorizontalABSTRACT
The unique extracellular electron transfer (EET) ability has positioned electroactive bacteria (EAB) as a major class of cellular chassis for genetic engineering aimed at favorable environmental, energy, and geoscience applications. However, previous efforts to genetically enhance EET ability have often impaired the basal metabolism and cellular growth due to the competition for the limited cellular resource. Here, we design a quorum sensing-based population-state decision (PSD) system for intelligently reprogramming the EET regulation system, which allows the rebalanced allocation of the cellular resource upon the bacterial growth state. We demonstrate that the electron output from Shewanella oneidensis MR-1 could be greatly enhanced by the PSD system via shifting the dominant metabolic flux from initial bacterial growth to subsequent EET enhancement (i.e., after reaching a certain population-state threshold). The strain engineered with this system achieved up to 4.8-fold EET enhancement and exhibited a substantially improved pollutant reduction ability, increasing the reduction efficiencies of methyl orange and hexavalent chromium by 18.8- and 5.5-fold, respectively. Moreover, the PSD system outcompeted the constant expression system in managing EET enhancement, resulting in considerably enhanced electron output and pollutant bioreduction capability. The PSD system provides a powerful tool for intelligently managing extracellular electron transfer and may inspire the development of new-generation smart bioelectrical devices for various applications.
Subject(s)
Electron Transport/physiology , Shewanella/physiology , Cell Respiration/physiology , Chromium/metabolism , Electrons , Quorum Sensing/physiology , Shewanella/metabolismABSTRACT
This study aimed to investigate more detailed functions of circ_0005276 in prostate cancer (PCa) and provide a novel mechanism for circ_0005276 action. The expression of circ_0005276, microRNA-128-3p (miR-128-3p) and DEP domain containing 1B (DEPDC1B) was detected by quantitative real-time PCR. In functional assays, cell proliferation was determined by CCK-8 assay and EdU assay. Cell migration and invasion were determined by transwell assay. The ability of angiogenesis was determined by tube formation assay. Cell apoptosis was determined by flow cytometry assay. The potential binding relationship between miR-128-3p and circ_0005276 or DEPDC1B was ascertained by dual-luciferase reporter assay and RIP assay. Mouse models were used to verify the role of circ_0005276 in vivo. The upregulation of circ_0005276 was determined in PCa tissues and cells. Circ_0005276 knockdown inhibited proliferation, migration, invasion and angiogenesis in PCa cells, and circ_0005276 knockdown also blocks tumor growth in vivo. Mechanism analysis discovered that miR-128-3p was a target of circ_0005276, and miR-128-3p inhibition recovered circ_0005276 knockdown-inhibited proliferation, migration, invasion and angiogenesis. In addition, DEPDC1B was a target of miR-128-3p, and miR-128-3p restoration-inhibited proliferation, migration, invasion and angiogenesis were rescued by DEPDC1B overexpression. Circ_0005276 might promote the development of PCa by activating the expression of DEPDC1B via targeting miR-128-3p.
Subject(s)
MicroRNAs , Prostatic Neoplasms , Animals , Mice , Male , Humans , Prostatic Neoplasms/genetics , Cell Movement , Cell Proliferation , Apoptosis , MicroRNAs/genetics , Cell Line, Tumor , GTPase-Activating ProteinsABSTRACT
OBJECTIVE: Ectopic pregnancy is a life-threatening disease and is an important cause of pregnancy-related mortality. MTX is the primary conservative treatment medicine of ectopic pregnancy, and mifepristone is also a promising medicine. Through studying the ectopic cases at the third affiliated hospital of Sun Yat-Sen University, the study aims to analyze the indication and treatment outcome predictors of mifepristone. METHODS: The data of 269 ectopic pregnancy cases treated with mifepristone during the year 2011-2019 were retrospectively collected. Logistic-regression analysis was used to analyze the factors affiliated with the treatment outcome of mifepristone. Then ROC curve was used to analyze the indication and predictors. RESULTS: Through logistic-regression analysis, HCG is the only factor related to the treatment outcome of mifepristone. The AUC of ROC curve predicting treatment outcome with pre-treatment HCG is 0.715, and the cutoff value of ROC curve is 372.66 (sensitivity 0.752, specificity 0.619). The AUC of 0/4 ratio predicting the treatment outcome is 0.886, and the cutoff value is 0.3283 (sensitivity 0.967, specificity 0.683). The AUC of 0/7 ratio is 0.947, and the cutoff value is 0.3609 (sensitivity 1, specificity 0.828). CONCLUSIONS: Mifepristone can be used to treat ectopic pregnancy. HCG is the only factor related to the treatment outcome of mifepristone. Patients with HCG less than 372.66 U/L can be treated by mifepristone. If HCG descends more than 67.18% on the 4th day or 63.91% on the 7th day, it is more likely to have a successful treatment outcome. It is more precise to retest on the 7th day.
Subject(s)
Mifepristone , Pregnancy, Ectopic , Pregnancy , Female , Humans , Mifepristone/therapeutic use , Retrospective Studies , Methotrexate , Pregnancy, Ectopic/drug therapy , Treatment Outcome , Chorionic Gonadotropin, beta Subunit, HumanABSTRACT
In area where α-thalassemia and ß-thalassemia are prevalent, the coinheritance of hemoglobin H disease (Hb H disease) and ß-thalassemia are not uncommon and could result in complex thalassemia intermedia syndromes. In this study, we investigate the hematological and molecular characteristics of two previously undescribed cases that co-inherited Hb H disease and rare ß-globin gene (HBB) mutations found in Chinese populations. Proband I was a boy with Hb H disease in association with IVS-II-5(G > C) (HBB:c0.315 + 5G > C) mutation. Proband II was a boy with a combination of Hb H and Hb Zengcheng [ß114(G16) Leu > Met; HBB:c.343C > A]. Both of them had mild hypochromic microcytic anemia, and neither had ever received a blood transfusion. In both cases, the level of Hb A2 was within normal range, and no Hb H was detected, but a small amount of Hb Bart's was observed in proband I. Routine DNA analysis detected the deletional Hb H disease in both cases. IVS-II-5(G > C) (HBB:c0.315 + 5G > C) and Hb Zengcheng (HBB:c.343C > A) mutations were found by DNA sequencing of ß-globin gene. The co-inheritance of Hb H disease with rare ß-thalassemia may result in an atypical pattern of Hb H disease, and further investigation of rare genotypes should be conducted to avoid missed diagnosis.
Subject(s)
alpha-Thalassemia , beta-Thalassemia , Humans , alpha-Thalassemia/diagnosis , alpha-Thalassemia/genetics , beta-Globins/genetics , beta-Thalassemia/diagnosis , beta-Thalassemia/genetics , Mutation , Phenotype , GenotypeABSTRACT
In this study, a red-green dual-emitting fluorescent composite (RhB@MOFs) was constructed by introducing the red-emitting organic fluorescent dye rhodamine B (RhB) into metal-organic frameworks (Tb-MOFs). The sample can be used as a ratiometric fluorescent probe, which not only avoids errors caused by instrument and environmental instability but also has multiple applications in detection. The results indicated that the RhB@MOFs exhibited a turned-off response toward Fe3+ and a turned-on response for the continuous detection of ascorbic acid (AA). This ratiometric fluorescent probe possessed high sensitivity and excellent selectivity in the continuous determination of Fe3+ and AA. It is worth mentioning that remarkable fluorescence change could be clearly observed by the naked eye under a UV lamp, which is more convenient in applications. In addition, the mechanisms of Fe3+- and AA-induced fluorescence quench and recovery are discussed in detail. This ratiometric probe displayed outstanding recognition of heavy metal ions and biomolecules, providing potential applications for water quality monitoring and biomolecule determination.
ABSTRACT
A novel fluorescent probe (C460@Tb-MOFs) was designed and synthesized by encapsulating the fluorescent dye 7-diethylamino-4-methyl coumarin (C460) into a terbium-based metal-organic framework using a simple ultrasonic impregnation method. It is impressive that this dye-modified metal-organic framework can specifically detect styrene and temperature upon luminescence quenching. The sensing platform of this material exhibits great selectivity, fast response, and good cyclability toward styrene detection. It is worth mentioning that the sensing process undergoes a distinct color change from blue to colorless, providing conditions for the accurate visual detection of styrene liquid and gas. The significant fluorescence quenching mechanism of styrene toward C460@Tb-MOFs is explored in detail. Moreover, the dye-modified metal-organic framework can also achieve temperature sensing from 298 to 498 K with high relative sensitivity at 498 K. The preparation of functionalized MOF composites with fluorescent dyes provides an effective strategy for the construction of sensors for multifunctional applications.