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Candidatus Accumulibacter, a key genus of polyphosphate-accumulating organisms, plays key roles in lab- and full-scale enhanced biological phosphorus removal (EBPR) systems. A total of 10 high-quality Ca. Accumulibacter genomes were recovered from EBPR systems operated at high temperatures, providing significantly updated phylogenetic and genomic insights into the Ca. Accumulibacter lineage. Among these genomes, clade IIF members SCELSE-3, SCELSE-4, and SCELSE-6 represent the to-date known genomes encoding a complete denitrification pathway, suggesting that Ca. Accumulibacter alone could achieve complete denitrification. Clade IIC members SSA1, SCUT-1, SCELCE-2, and SCELSE-8 lack the entire set of denitrifying genes, representing to-date known non-denitrifying Ca. Accumulibacter. A pan-genomic analysis with other Ca. Accumulibacter members suggested that all Ca. Accumulibacter likely has the potential to use dicarboxylic amino acids. Ca. Accumulibacter aalborgensis AALB and Ca. Accumulibacter affinis BAT3C720 seemed to be the only two members capable of using glucose for EBPR. A heat shock protein Hsp20 encoding gene was found exclusively in genomes recovered at high temperatures, which was absent in clades IA, IC, IG, IIA, IIB, IID, IIG, and II-I members. High transcription of this gene in clade IIC members SCUT-2 and SCUT-3 suggested its role in surviving high temperatures for Ca. Accumulibacter. Ambiguous clade identity was observed for newly recovered genomes (SCELSE-9 and SCELSE-10). Five machine learning models were developed using orthogroups as input features. Prediction results suggested that they belong to a new clade (IIK). The phylogeny of Ca. Accumulibacter was re-evaluated based on the laterally derived polyphosphokinase 2 gene, showing improved resolution in differentiating different clades.
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Carbon source is a key factor determining the denitrifying effectiveness and efficiency in wastewater treatment plants (WWTPs). Whereas, the relationships between diverse and distinct denitrifying communities and their favorable carbon sources in full-scale WWTPs were not well-understood. This study performed a systematic analysis of the relationships between the denitrifying community and carbon sources by using 15 organic compounds from four categories and activated sludge from 8 full-scale WWTPs. Results showed that, diverse denitrifying bacteria were detected with distinct relative abundances in 8 WWTPs, such as Haliangium (1.98-4.08%), Dechloromonas (2.00-3.01%), Thauera (0.16-1.06%), Zoogloea (0.09-0.43%), and Rhodoferax (0.002-0.104%). Overall, acetate resulted in the highest denitrifying activities (1.21-4.62 mg/L/h/gMLSS), followed by other organic acids (propionate, butyrate and lactate, etc.). Detectable dissimilatory nitrate reduction to ammonium (DNRA) was observed for all 15 carbon sources. Methanol and glycerol resulted in the highest DRNA. Acetate, butyrate, and lactate resulted in the lowest DNRA. Redundancy analysis and 16S cDNA amplicon sequencing suggested that carbon sources within the same category tended to correlate to similar denitrifiers. Methanol and ethanol were primarily correlated to Haliangium. Glycerol and amino acids (glutamate and aspartate) were correlated to Inhella and Sphaerotilus. Acetate, propionate, and butyrate were positively correlated to a wide range of denitrifiers, explaining the high efficiency of these carbon sources. Additionally, even within the same genus, different amplicon sequence variants (ASVs) performed distinctly in terms of carbon source preference and denitrifying capabilities. These findings are expected to benefit carbon source formulation and selection in WWTPs.
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Carbono , Desnitrificación , Eliminación de Residuos Líquidos , Aguas Residuales , Aguas Residuales/química , Aguas Residuales/microbiología , Carbono/metabolismo , Eliminación de Residuos Líquidos/métodos , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética , Aguas del Alcantarillado/microbiología , Nitratos/metabolismo , Nitratos/análisis , Compuestos de Amonio/metabolismoRESUMEN
Fluorescence in situ hybridization (FISH) and 16S rRNA gene amplicon sequencing are commonly used for microbial ecological analyses in biological enhanced phosphorus removal (EBPR) systems, the successful application of which was governed by the oligonucleotides used. We performed a systemic evaluation of commonly used probes/primers for known polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs). Most FISH probes showed blind spots and covered nontarget bacterial groups. Ca. Competibacter probes showed promising coverage and specificity. Those for Ca. Accumulibacter are desirable in coverage but targeted out-group bacteria, including Ca. Competibacter, Thauera, Dechlorosoma, and some polyphosphate-accumulating Cyanobacteria. Defluviicoccus probes are good in specificity but poor in coverage. Probes targeting Tetrasphaera or Dechloromonas showed low coverage and specificity. Specifically, DEMEF455, Bet135, and Dech453 for Dechloromonas covered Ca. Accumulibacter. Special attentions are needed when using these probes to resolve the PAO/GAO phenotype of Dechloromonas. Most species-specific probes for Ca. Accumulibacter, Ca. Lutibacillus, Ca. Phosphoribacter, and Tetrasphaera are highly specific. Overall, 1.4% Ca. Accumulibacter, 9.6% Ca. Competibacter, 43.3% Defluviicoccus, and 54.0% Dechloromonas in the MiDAS database were not covered by existing FISH probes. Different 16S rRNA amplicon primer sets showed distinct coverage of known PAOs and GAOs. None of them covered all members. Overall, 520F-802R and 515F-926R showed the most balanced coverage. All primers showed extremely low coverage of Microlunatus (<36.0%), implying their probably overlooked roles in EBPR systems. A clear understanding of the strength and weaknesses of each probe and primer set is a premise for rational evaluation and interpretation of obtained community results.
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The imbalance between endogenous and exogenous healing is the fundamental reason for the poor tendon healing. In this study, a Janus patch was developed to promote endogenous healing and inhibit exogenous healing, leading to improved tendon repair. The upper layer of the patch is a poly(dl-lactide-co-glycolide)/polycaprolactone (PLGA/PCL) nanomembrane (PMCP-NM) modified with poly(2-methylacryloxyethyl phosphocholine) (PMPC), which created a lubricated and antifouling surface, preventing cell invasion and mechanical activation. The lower layer is a PLGA/PCL fiber membrane loaded with fibrin (Fb) (Fb-NM), serving as a temporary chemotactic scaffold to regulate the regenerative microenvironment. In vitro, the Janus patch effectively reduced 92.41% cell adhesion and 79.89% motion friction. In vivo, the patch inhibited tendon adhesion through the TGF-ß/Smad signaling pathway and promoted tendon maturation. This Janus patch is expected to provide a practical basis and theoretical guidance for high-quality soft tissue repair.
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Tendones , Cicatrización de Heridas , Tendones/fisiología , Adhesión CelularRESUMEN
Due to the limitations of tendon biology, high-quality tendon repair remains a clinical and scientific challenge. Here, a micro-nano hierarchical scaffold is developed to promote orderly tendon regeneration by providing temporal-matched biological constraints. In short, fibrin (Fb), which provides biological constraints, is loaded into poly (DL-lactide-co-glycolide) nanoyarns with suitable degradation cycles (Fb-loaded nanofiber yarns (Fb-NY)). Then further combined with braiding technology, temporary chemotactic Fb scaffolds with tendon extracellular matrix-like structures are obtained to initiate the regeneration process. At the early stage of healing (2 w), the regeneration microenvironment is regulated (inducing M2 macrophages and restoring the early blood supply necessary for healing) by Fb, and the alignment of cells and collagen is induced by nanoyarn. At the late healing stage (8 w), with the degradation of Fb-NY, non-functional vascular regression occurs, and the newborn tissues gradually undergo load-bearing remodeling, restoring the anvascularous and ordered structure of the tendon. In summary, the proposed repair strategy provides temporal-matched biological constraints, offering a potential pathway to reconstruct the ordered structure and function of tendons.
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Nanofibras , Andamios del Tejido , Recién Nacido , Humanos , Andamios del Tejido/química , Colágeno/química , Tendones , Matriz Extracelular/metabolismo , Ingeniería de TejidosRESUMEN
Recently, examples of metal-organic frameworks (MOFs) have been identified displaying ethane (C2H6) over ethylene (C2H4) adsorption selectivity. However, it remains a challenge to construct MOFs with both large C2H6 adsorption capacity and high C2H6/C2H4 adsorption selectivity, especially under humid conditions. Herein, we reported two isoreticular MOF-5 analogues (JNU-6 and JNU-6-CH3) and their potential applications in one-step separation of C2H4 from C2H6/C2H4 mixtures. The introduction of CH3 groups not only reduces the pore size from 5.4 Å in JNU-6 to 4.1 Å in JNU-6-CH3 but also renders an increased electron density on the pyrazolate N atoms of the organic linker. JNU-6-CH3 retains its framework integrity even after being immersed in water for six months. More importantly, it exhibits large C2H6 adsorption capacity (4.63 mmol g-1) and high C2H6/C2H4 adsorption selectivity (1.67) due to the optimized pore size and surface function. Breakthrough experiments on JNU-6-CH3 demonstrate that C2H4 can be directly separated from C2H6/C2H4 (50/50, v/v) mixtures, affording benchmark productivity of 22.06 and 18.71 L kg-1 of high-purity C2H4 (≥99.95%) under dry and humid conditions, respectively.
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Previous research suggested that two major groups of polyphosphate-accumulating organisms (PAOs), i.e., Ca. Accumulibacter and Tetrasphaera, play cooperative roles in enhanced biological phosphorus removal (EBPR). The fermentation of complex organic compounds by Tetrasphaera provides carbon sources for Ca. Accumulibacter. However, the viability of the fermentation products (e.g., lactate, succinate, alanine) as carbon sources for Ca. Accumulibacter and their potential effects on the metabolism of Ca. Accumulibacter were largely unknown. This work for the first time investigated the capability and metabolic details of Ca. Accumulibacter cognatus clade IIC strain SCUT-2 (enriched in a lab-scale reactor with a relative abundance of 42.8%) in using these fermentation products for EBPR. The enrichment culture was able to assimilate lactate and succinate with the anaerobic P release to carbon uptake ratios of 0.28 and 0.36 P mol/C mol, respectively. In the co-presence of acetate, the uptake of lactate was strongly inhibited, since two substrates shared the same transporter as suggested by the carbon uptake bioenergetic analysis. When acetate and succinate were fed at the same time, Ca. Accumulibacter assimilated two carbon sources simultaneously. Proton motive force (PMF) was the key driving force (up to 90%) for the uptake of lactate and succinate by Ca. Accumulibacter. Apart from the efflux of proton in symport with phosphate via the inorganic phosphate transport system, translocation of proton via the activity of fumarate reductase contributed to the generation of PMF, which agreed with the fact that PHV was a major component of PHA when lactate and succinate were used as carbon sources, involving the succinate-propionate pathway. Metabolic models for the usage of lactate and succinate by Ca. Accumulibacter for EBPR were built based on the combined physiological, biochemical, metagenomic, and metatranscriptomic analyses. Alanine was shown as an invalid carbon source for Ca. Accumulibacter. Instead, it significantly and adversely affected Ca. Accumulibacter-mediated EBPR. Phosphate release was observed without alanine uptake. Significant inhibitions on the aerobic phosphate uptake was also evident. Overall, this study suggested that there might not be a simply synergic relationship between Ca. Accumulibacter and Tetrasphaera. Their interactions would largely be determined by the kind of fermentation products released by the latter.
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Betaproteobacteria , Fósforo , Fósforo/metabolismo , Fermentación , Protones , Reactores Biológicos , Betaproteobacteria/metabolismo , Polifosfatos/metabolismo , Lactatos/metabolismo , Alanina , Succinatos/metabolismo , Carbono/metabolismo , Acetatos/metabolismoRESUMEN
Pancreatic cancer (PC) is one of the most common malignant tumors in digestive tract. To explore the role of epigenetic factor EZH2 in the malignant proliferation of PC, so as to provide effective medical help in PC. Sixty paraffin sections of PC were collected and the expression of EZH2 in PC tissues was detected by immunohistochemical assay. Three normal pancreas tissue samples were used as controls. The regulation of EZH2 gene on proliferation and migration of normal pancreatic cell and PC cell were determined by MTS, colony forming, Ki-67 antibody, scratch and Transwell assays. Through differential gene annotation and differential gene signaling pathway analysis, differentially expressed genes related to cell proliferation were selected and verified by RT-qPCR. EZH2 is mainly expressed in the nuclei of pancreatic tumor cells, but not in normal pancreatic cells. The results of cell function experiments showed that EZH2 overexpression could enhance the proliferation and migration ability of PC cell BXPC-3. Cell proliferation ability increased by 38% compared to the control group. EZH2 knockdown resulted in reduced proliferation and migration ability of cells. Compared with control, proliferation ability of cells reduced by 16%-40%. The results of bioinformatics analysis of transcriptome data and RT-qPCR demonstrated that EZH2 could regulate the expression of E2F1, GLI1, CDK3 and Mcm4 in normal and PC cells. The results revealed that EZH2 might regulate the proliferation of normal pancreatic cell and PC cell through E2F1, GLI1, CDK3 and Mcm4.
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Neoplasias Pancreáticas , Humanos , Proteína con Dedos de Zinc GLI1/metabolismo , Línea Celular Tumoral , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Páncreas/metabolismo , Páncreas/patología , Componente 4 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Quinasa 3 Dependiente de Ciclina/metabolismo , Factor de Transcripción E2F1/metabolismo , Neoplasias PancreáticasRESUMEN
Natural vegetation has been proved to promote water purification in previous studies, while the relevant laws has not been excavated systematically. This research explored the relationships between vegetation cover and water quality indexes in Liaohe River Basin in China combined with self-organizing map (SOM) and geographically and temporally weighted regression (GTWR) innovatively and systematically based on the distributing heterogeneity of water quality conditions. Results showed that the central and northeast regions of the study area had serious organic and nutrient pollution, which needed targeted treatment. And SOM verified that high vegetation coverage with retention potential of organic and inorganic pollutants as well as nutrients improved water quality to some degree, while the excessive discharges of pollutants still had serious threats to nearby water environment despite the purification function of vegetation. GTWR indicated that the waterside vegetation was beneficial for dissolved oxygen increasing and contributed to the decreasing of organic pollutants and inorganic pollutants with reducibility. Natural vegetation also obsorbed nutrients like TN and TP to some degree. However, the retential potential of nitrogen and organic pollutants became not obvious when there were heavy pollution, which demonstrated that pollution sources should be controlled despite the purification function of vegetation. This study implied that natural vegetation purified water quality to some degree, while this function could not be revealed when there was too heavy pollution. These findings underscore that the pollutant discharge should be controlled though the natural vegetation in ecosystem promoted the purification of water bodies.
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Contaminantes Químicos del Agua , Calidad del Agua , Monitoreo del Ambiente/métodos , Fósforo/análisis , Ecosistema , Contaminantes Químicos del Agua/análisis , Ríos , Nitrógeno/análisis , ChinaRESUMEN
The efficient separation of acetylene (C2H2) from its mixture with carbon dioxide (CO2) remains a challenging industrial process due to their close molecular sizes/shapes and similar physical properties. Herein, we report a microporous metal-organic framework (JNU-4) with square-planar mononuclear copper(ii) centers as nodes and tetrahedral organic linkers as spacers, allowing for two accessible binding sites per metal center for C2H2 molecules. Consequently, JNU-4 exhibits excellent C2H2 adsorption capacity, particularly at 298 K and 0.5 bar (200 cm3 g-1). Detailed computational studies confirm that C2H2 molecules are indeed predominantly located in close proximity to the square-planar copper centers on both sides. Breakthrough experiments demonstrate that JNU-4 is capable of efficiently separating C2H2 from a 50 : 50 C2H2/CO2 mixture over a broad range of flow rates, affording by far the largest C2H2 capture capacity (160 cm3 g-1) and fuel-grade C2H2 production (105 cm3 g-1, ≥98% purity) upon desorption. Simply by maximizing accessible open metal sites on mononuclear metal centers, this work presents a promising strategy to improve the C2H2 adsorption capacity and address the challenging C2H2/CO2 separation.
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BACKGROUND: One in six older adults living in communities experience abuse and neglect. Elder abuse has serious consequences for individuals, families, and society, including mortality, physical and psychological morbidities, and increased care requirements. Timely and effective interventions for elder abuse should therefore be a priority. This study used a qualitative focus group approach to address the following questions: What are the essential elements of elder abuse interventions? What can be done to improve current interventions? METHOD: The 32 participants in this focus group study included social workers, medical social workers, and nurses from seven organizations who shared their knowledge and insights. All sessions were conducted online, audio-recorded, and transcribed verbatim. Three researchers with backgrounds in social work and psychology independently coded the transcripts and agreed on the themes emerging from the focus groups. RESULTS: Based on the experiences of frontline helping professionals in Hong Kong, we highlighted the key factors for effective elder abuse intervention: 1) identification and assessment; 2) essential skills and attitudes; 3) elements of effective interventions; 4) collaborative efforts across disciplines and agencies; and 5) raising awareness among professionals and the public. CONCLUSIONS: Training can equip frontline professionals with the necessary skills to identify elder abuse cases and to assess the risk of abuse. Effective interventions should not only address clients' safety and need for tangible support but also respect their autonomy and privacy. A client-centered, strength-based approach that involves supportive peers and addresses the complex family relationships involved can be useful. Interventions should also involve cross-discipline and cross-agency collaboration.
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Abuso de Ancianos , Humanos , Anciano , Grupos Focales , Abuso de Ancianos/psicología , Hong Kong , Servicio Social , Trabajadores Sociales/psicologíaRESUMEN
Ligament regeneration is a complicated process that requires dynamic mechanical properties and allowable space to regulate collagen remodeling. Poor strength and limited space of currently available grafts hinder tissue regeneration, yielding a disappointing success rate in ligament reconstruction. Matching the scaffold retreat rate with the mechanical and spatial properties of the regeneration process remains challenging. Herein, a scaffold matching the regeneration process was designed via regulating the trajectories of fibers with different degradation rates to provide dynamic mechanical properties and spatial adaptability for collagen infiltration. This core-shell structured scaffold exhibited biomimetic fiber orientation, having tri-phasic mechanical behavior and excellent strength. Besides, by the sequential material degradation, the available space of the scaffold increased from day 6 and remained stable on day 24, consistent with the proliferation and deposition phase of the native ligament regeneration process. Furthermore, mature collagen infiltration and increased bone integration in vivo confirmed the promotion of tissue regeneration by the adaptive space, maintaining an excellent failure load of 67.65% of the native ligament at 16 weeks. This study proved the synergistic effects of dynamic strength and adaptive space. The scaffold matching the regeneration process is expected to open new approaches in ligament reconstruction.
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Background and Aims: To compare the effects of real-time and retrospective flash glucose monitoring (FGM) on daily glycemic control and lifestyle in patients with type 2 diabetes on premix insulin therapy. Methods and Results: A total of 172 patients using premix insulin, with HbA1c ≥ 7.0% (56 mmol/mol), or the time below the target (TBR) ≥ 4%, or the coefficient of variation (CV) ≥36% during the screening period, were randomly assigned to retrospective FGM (n = 89) or real-time FGM group (n = 83). Another two retrospective or real-time 14-day FGMs were performed respectively, 1 month apart. Both groups received educations and medication adjustment after each FGM. Time in range (3.9~10.0 mmol/l, TIR) increased significantly after 3 months in the real-time FGM group (6.5%) compared with the retrospective FGM group (-1.1%) (p = 0.014). HbA1c decreased in both groups (both p < 0.01). Real-time FGMs increased daily exercise time compared with the retrospective group (p = 0.002). Conclusions: Real-time FGM with visible blood glucose improves daily glycemic control and diabetes self-care behaviors better than retrospective FGM in patients with type 2 diabetes on premix insulin therapy. Clinical Trial Registration: https://clinicaltrials.gov/NCT04847219.
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Insulinas Bifásicas/uso terapéutico , Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Control Glucémico , Anciano , Glucemia/análisis , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana EdadRESUMEN
Rigid molecular sieving materials work well for small molecules with the complete exclusion of large ones1-3, and molecules with matching physiochemical properties may be separated using dynamic molecular sieving materials4-6. Metal-organic frameworks (MOFs)7-9 are known for their precise control of structures and functions on a molecular level10-15. However, the rational design of local flexibility in the MOF framework for dynamic molecular sieving remains difficult and challenging. Here we report a MOF material (JNU-3a) featuring one-dimension channels with embedded molecular pockets opening to propylene (C3H6) and propane (C3H8) at substantially different pressures. The dynamic nature of the pockets is revealed by single-crystal-to-single-crystal transformation upon exposure of JNU-3a to an atmosphere of C3H6 or C3H8. Breakthrough experiments demonstrate that JNU-3a can realize high-purity C3H6 (≥99.5%) in a single adsorption-desorption cycle from an equimolar C3H6/C3H8 mixture over a broad range of flow rates, with a maximum C3H6 productivity of 53.5 litres per kilogram. The underlying separation mechanism-orthogonal-array dynamic molecular sieving-enables both large separation capacity and fast adsorption-desorption kinetics. This work presents a next-generation sieving material design that has potential for applications in adsorptive separation.
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BACKGROUND: The purpose of this study was to construct a new typing model for diffuse large B-cell lymphoma (DLBCL) patients based on the B-cell receptor (BCR) and explore its potential molecular mechanism. METHODS: BCR repertoire sequencing and whole-exome sequencing were performed on formalin-fixed paraffin-embedded samples from 12 DLBCL patients. Subsequently, a typing model was built with cluster analysis, and prognostic indicators between the two groups were compared to verify the typing model. Then, mutation and bioinformatics analyses were conducted to investigate the potential biomarkers of prognostic differences between the two groups. RESULTS: Based on BCR sequencing data, we divided patients into two clusters (cluster 1 and cluster 2); this classification differed from the traditional typing method (GCB and non-GCB), in which cluster 1 included some non-GCB patients. The progression-free survival (PFS), overall survival (OS), metastasis and Shannon diversity index of IGH V-J and survival after chemotherapy were significantly different (P < 0.05) between the two clusters, but no statistical significance was found between the GCB and non-GCB groups. The mutation status of 248 genes was significantly different between cluster 1 and cluster 2. Among them, FTSJ3, MAGED2, and ODF3L2 were the specific mutated genes in all patients in cluster 2, and these genes could be considered critical to the different prognoses of the two clusters of DLBCL patients. CONCLUSION: We constructed a new typing model of DLBCL based on BCR repertoire sequencing that can better predict the survival time after chemotherapy. FTSJ3, MAGED2, and ODF3L2 may represent key genes for the difference in prognosis between the two clusters.
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Linfoma de Células B Grandes Difuso/genética , Receptores de Antígenos de Linfocitos B/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Anciano , Antígenos de Neoplasias/genética , Análisis por Conglomerados , Femenino , Humanos , Linfoma de Células B Grandes Difuso/clasificación , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Metiltransferasas/genética , Persona de Mediana Edad , Mutación , Pronóstico , Proteínas de Plasma Seminal/genética , Secuenciación del ExomaRESUMEN
Aim: To explore the chronic effects of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM). Methods: This is a secondary analysis of a real-world study evaluating the efficacy and safety of premixed insulin treatment in patients with T2DM via 3-month intermittent flash glucose monitoring. Male patients aged 18-60 who were using metformin during the 3-month study period were included as the metformin group. The control group included males without metformin therapy by propensity score matching analysis with age as a covariate. Testosterone levels were measured at baseline and after 3-month treatment. Results: After 3-month treatment, the control group had higher levels of total testosterone, free and bioavailable testosterone than those at baseline (P<0.05). Compared with the control group, the change of total (-0.82 ± 0.59 vs. 0.99 ± 0.59 nmol/L) and bioavailable (-0.13 ± 0.16 vs. 0.36 ± 0.16 nmol/L) testosterone levels in the metformin group significantly decreased (P=0.036 and 0.029, respectively). In Glycated Albumin (GA) improved subgroup, the TT, FT, and Bio-T levels in the control subgroup were higher than their baseline levels (P < 0.05). Compared with the metformin subgroup, TT level in the control subgroup also increased significantly (P=0.044). In GA unimproved subgroup, the change of TT level in the metformin subgroup was significantly lower than that in the control subgroup (P=0.040). Conclusion: In men with T2DM, 3-month metformin therapy can reduce testosterone levels, and counteract the testosterone elevation that accompanied with the improvement of blood glucose. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT04847219?term=04847219&draw=2&rank=1.
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Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Metformina/administración & dosificación , Testosterona/sangre , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Testosterona/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
C2 separation is of great importance in the petrochemical industry. Traditionally, it is performed by distillation at cryogenic temperatures, which necessitates the consumption of a huge amount of energy to operate the refrigeration system in the production process. In this regard, it is imperative to seek alternative separation methods with high efficiency and low energy cost. Although of recent origin, metal-organic frameworks (MOFs) have already been extensively studied as advanced adsorbents in many applications, and significant progress has been made particularly in gas separation owing to their unprecedented porosity and tunable structures. In this review, we extrapolated three most frequently invoked design strategies for efficient C2 separation hinged upon supramolecular interactions, including molecular sieving, gate opening, and surface engineering. Recent progress of MOF materials in C2 separation was highlighted within each of these strategies, and their advantages and limitations are compared and discussed. Accordingly, we provide perspectives on current challenges and future emphases in designing MOF materials for hydrocarbon separation. With our continued efforts in this area, we expect that integrating supramolecular interactions in a single MOF system is a viable approach to achieve a balance between adsorption capacity and selectivity for different hydrocarbon separation scenarios.
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Hereditary spherocytosis (HS) is often misdiagnosed due to lack of specific diagnostic methods. Our study summarized clinical characteristics and described the diagnostic workflow for mild and moderate HS in Chinese individuals, using data from 20 adults, 8 of whom presented a familial history for HS. We used scanning electron microscopy (SEM) to diagnose HS. We observed reduced eosin maleimide fluorescence activity (5.50 mean channel fluorescence (MCF) units) in the 10 cases of HS, which differed significantly when compared with 10 normal adults (15.50 units), iron deficiency anemia (15.50 MCF units), and megaloblastic anemia (12.00 MCF units) values (P < .05). Next generation sequencing results revealed that 9 out of 10 patients were found to have mutations in the spectrin alpha chain (SPTB), anchor protein (ANK1), and SLC4A1 genes. These mutations were not reported in the Human Gene Mutation Database (HGMD), 1000 human genome, ExAC, and dbSNP147 databases. Splenectomy proved to be beneficial in alleviating HS symptoms in 10 cases. It was found that for the diagnosis of HS, SEM and next generation gene sequencing method proved to be more ideal than red blood cell membrane protein analysis using sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting.
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Anemia Ferropénica/diagnóstico , Anemia Megaloblástica/diagnóstico , Proteína 1 de Intercambio de Anión de Eritrocito/genética , Ancirinas/genética , Espectrina/genética , Esferocitosis Hereditaria/diagnóstico , Adolescente , Adulto , Anciano , Anemia Ferropénica/etnología , Anemia Ferropénica/genética , Anemia Megaloblástica/etnología , Anemia Megaloblástica/genética , Pueblo Asiatico , Biomarcadores/metabolismo , Estudios de Casos y Controles , Diagnóstico Diferencial , Eosina Amarillenta-(YS)/análogos & derivados , Eosina Amarillenta-(YS)/química , Femenino , Colorantes Fluorescentes/química , Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Mutación , Esferocitosis Hereditaria/etnología , Esferocitosis Hereditaria/genética , Esferocitosis Hereditaria/cirugía , Esplenectomía/métodosRESUMEN
BACKGROUND: The present study aimed to use the targeted capture and sequencing technique to diagnose adult hereditary spherocytosis (HS). These results were compared with clinical features and laboratory examinations to explore the diagnosis of HS. METHODS: Whole blood and clinical data from ten patients with HS were collected. Genomic DNA was extracted, and a library was prepared. Exomes of patients with ten HS-related genes encoding red cell membrane skeleton protein were captured and sequenced. Bioinformatics analyses were carried out throughout the 1000 Genomes Project, ExAC, dbSNP147, and 1000 Normal Han Population databases. RESULTS: Gene mutations were found in 9 out of 10 cases of HS. Our data validation showed 90% specificity. Three types of gene mutations were found, including 6 cases of SPTB, 3 cases of ANK1, and 2 cases of SLC4A1. There were 4 mutation forms, including nonsense mutation, missense mutation, shear mutation, and code shift mutation, all of which were new, heterozygous mutations. These variations were predicted to be pathogenic in four databases. CONCLUSIONS: Our data demonstrate that targeted gene enrichment and sequencing methods were an efficient tool for determining genetic etiologies of red blood cell (RBC) membrane disorders and can facilitate accurate diagnosis and genetic counseling. They are also in good agreement with the clinical results.
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Metal-organic frameworks (MOFs) with open metal sites (OMSs) have been shown to preferentially adsorb unsaturated hydrocarbons such as C2H4 due to the formation of π-complexation. However, the adsorption capacity and selectivity might well be dampened under humid conditions because OMSs could be easily poisoned in the presence of water vapor. C2H6-selective adsorbents with less hydrophilic environments, on the other hand, not only could effectively minimize the impact of humidity on separation capacity but also could directly produce high-purity C2H4 from C2H6/C2H4 mixtures. Here, we report a C2H6-selective MOF (JNU-2) underlying a rare xae topology. Its cage-like cavities are interconnected through apertures with a limiting diameter of ca. 3.7 Å, which is in the domain of kinetic diameters of C2H4 and C2H6 molecules. Molecular modeling studies suggest the four oxygen atoms on aperture are poised to preferentially interact with C2H6 through multiple C-H···O hydrogen bonding, rendering JNU-2 an enhanced C2H6 selectivity. Indeed, experimental results reveal that JNU-2 not only takes up a great amount of C2H6 comparable to other top-performing C2H6-selective MOFs but also displays excellent separation capacity even under humid conditions; moreover, it can be easily regenerated at room temperature owing to its moderate adsorption enthalpy. This work successfully demonstrated a strategy of balancing adsorption capacity and selectivity for C2H6 by designing MOF materials with cavities interconnected through tailored apertures. The apertures function as screening sites for C2H6 selectivity, while the internal cavities provide space for large adsorption.