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The authors report a case of primary aldosteronism (PA) with postoperative elevation of aldosterone treated effectively by finerenone. The patient was a hypertensive man with a 30-year history of hypertension and sustained an acute myocardial infarction 5 years ago. Bilateral adrenal nodules with hyperplasia were detected and PA was confirmed. His blood potassium, direct renin concentration, and aldosterone level returned to normal after surgery of right adrenalectomy. However, 1 year after surgery, he experienced a decrease in blood potassium and an increase in aldosterone. A saline infusion test revealed an aldosterone level of 124.47 pg/mL. The patient consented to treatment with finerenone. His aldosterone and potassium levels and blood pressure have been controlled well during follow-up. This case highlights the need to screen for secondary hypertension as early as possible. Finerenone may be effective for patients with PA who are not candidates for surgery and those not relieved after surgery.
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Sleep quality is crucial for the personal well-being of healthcare professionals and the health outcomes of their patients. This study aims to explore the relationship between psychological resilience (PR), perceived social support (PSS), psychological distress (comprising anxiety,depression,and stress), and sleep quality. It also examines whether PSS and psychological distress function as chain mediators between PR and sleep quality. A cross-sectional online survey was conducted using a convenient sampling method, with 454 participants included. The survey instruments included the Connor and Davidson Resilience Scale, the Perceived Social Support Scale, the 21-item Depression Anxiety Stress Scale, and the Pittsburgh Sleep Quality Index. Structural equation modeling revealed that PR significantly predicted sleep quality of Chinese medical staff. Psychological distress was identified as a mediating factor between PR and sleep quality. However, PSS did not directly mediate the relationship between PR and sleep quality. Instead, PSS and psychological distress were found to play a chain mediating role in the relationship between PR and sleep quality. This study provides new insights into the impact of PR on sleep quality, highlights the importance of PSS and psychological distress, and suggests practical implications for enhancing sleep quality among medical staff.
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Angústia Psicológica , Resiliência Psicológica , Qualidade do Sono , Apoio Social , Humanos , Feminino , Masculino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , China/epidemiologia , Inquéritos e Questionários , Corpo Clínico/psicologia , Estresse Psicológico/psicologia , Depressão/psicologia , Depressão/epidemiologia , Adulto Jovem , Ansiedade/psicologia , População do Leste AsiáticoRESUMO
Flower endophytic fungi play a major role in plant reproduction, stress resistance, and growth and development. However, little is known about how artificial cultivation affects the endophytic fungal community found in the tepals of rare horticultural plants. In this research, we used high-throughput sequencing technology combined with bioinformatics analysis to reveal the endophytic fungal community of tepals in Lirianthe delavayi and the effects of artificial cultivation on the community composition and function of these plants, using tepals of L. delavayi from wild habitat, cultivated campus habitat, and cultivated field habitat as research objects. The results showed that the variety of endophytic fungi in the tepals of L. delavayi was abundant, with a total of 907 Amplicon sequencing variants (ASVs) obtained from all the samples, which were further classified into 4 phyla, 23 classes, 51 orders, 97 families, 156 genera, and 214 species. We also found that artificial cultivation had a significant impact on the community composition of endophytic fungi. Although there was no significant difference at the phylum level, with Ascomycota and Basidiomycota being the main phyla, there were significant differences in dominant and unique genera. Artificial cultivation has led to the addition of new pathogenic fungal genera, such as Phaeosphaeria, Botryosphaeria, and Paraconiothyrium, increasing the risk of disease in L. delavayi. In addition, the abundance of the endophytic fungus Rhodotorula, which is typical in plant reproductive organs, decreased. Artificial cultivation also altered the metabolic pathways of endophytic fungi, decreasing their ability to resist pests and diseases and reducing their ability to reproduce. A comparison of endophytic fungi in tepals and leaves revealed significant differences in community composition and changes in the endophytic diversity caused by artificial cultivation. To summarize, our results indicate that endophytic fungi in the tepals of L. delavayi mainly consist of pathogenic and saprophytic fungi. Simultaneously, artificial cultivation introduces a great number of pathogenic fungi that alter the metabolic pathways associated with plant resistance to disease and pests, as well as reproduction, which can increase the risk of plant disease and reduce plant reproductive capacity. Our study provides an important reference for the conservation and breeding of rare horticultural plants.
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With the wide application of electromagnetic waves in national defense, communication, navigation and home appliances, the electromagnetic pollution problem is becoming more and more prominent. Therefore, high-performance, and low-density composite wave-absorbing materials have attracted much attention. In this paper, three-dimensional (3D) network structures of flower-like 1T/2H Molybdenum disulfide nanosheets anchored to carbon fibers (1T/2H MoS2/CNFs) were prepared by electrostatic spinning technique and calcination process. The morphology and electromagnetic wave absorption properties were tuned by changing the content of flower-like MoS2. The optimized 1T/2H MoS2/CNFs composite exhibits superior electromagnetic wave absorption with minimum reflection (RLmin) of -42.26 dB and effective absorption bandwidth (EAB) of 6.48 GHz at 2.5 mm. Multi-facts contribute to the super performance. First, the uniquely designed nanosheet and 3D interconnected networks leads to multiple reflection and scattering of electromagnetic waves, which promotes the attenuation of electromagnetic waves. Second, the propriate content of CNFs and MoS2 with different phase regulates its impedance matching characteristic. Third, Numerous heterogeneous interfaces existed between CNFs and MoS2, 1T and 2H MoS2 phase results in interface polarization. Besides, the 1T/2H MoS2 rich in defects induces defect polarization, improving the dielectric loss. Furthermore, the electromagnetic wave absorption performance was proved via radar reflectance cross section simulation. This work illustrates 1T/2H MoS2/CNFs is a promising material for electromagnetic absorption with wide bandwidth, strong absorption, low density, and high thermal stability.
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Although TiNb2O7 (TNO) with comparable operating potential and ideal theoretical capacity is considered to be the most ideal replacement for negative Li4Ti5O12 (LTO), the low ionic and electronic conductivity still limit its practical application as satisfactory anode for lithium-ion batteries (LIBs) with high-power density. Herein, TNO nanoparticles modified by Cerium (Ce) with outstanding electrochemical performance are synthesized. The successful introduction of Ce3+ in the lattice leads to increased interplanar spacing, refined grain size, more oxygen vacancy, and a smaller lithium diffusion barrier, which are conducive to improve conductivity of both Li+ and electrons. As a result, the modified TNO reaches high reversible capacity of 256.0 mA h g-1 at 100 mA g-1 after 100 cycles, and 183.0 mA h g-1 even under 3200 mA g-1. In particular, when the temperature drops to -20 °C, the cell undergoing 1500 cycles at a high current density of 500 mA g-1 can still reach 89.7 mA h g-1, corresponding to a capacity decay rate per cycle of only 0.033%. This work provides a new way to improve the electrochemical properties of alternative anodes for LIBs at extreme temperature.
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Developing efficient and low-cost photocatalytic materials is essential for removing polychlorinated biphenyls (PCBs). In this work, the photodegradation process of fourteen representative polychlorinated biphenyls (PCBs) in both water/nitrogen-doped SiO2 (N-SiO2) and air/N-SiO2 systems was studied. The photodegradation kinetics of PCBs is consistent with the pseudo-first-order kinetic equation. The variation in the degradation effects of different PCBs in the two systems is primarily related to the position of the Cl substituent and the effective absorption wavelength range of PCBs. A total of fourteen intermediates for 4'-Dichlorobiphenyl (PCB-15), 2,2',4,4',6,6'-Hexachlorobiphenyl (PCB-155), and 2,2',3,3',4,4',5,5',6,6'-Decachlorobiphenyl (PCB-209) generated from four reaction pathways were identified based on both mass spectrometry analysis and theoretical calculations. Using the values of lnk (k denotes pseudo-first-order kinetic constants) for the 11 PCBs in the training set and the calculated molecular and structural parameters, quantitative structure-activity relationship (QSAR) models for the two systems were constructed by using multiple linear regression (MLR) method to better understand the factors affecting the photodegradation rate of PCBs. The QSAR equations were obtained with Cl atom substitution at position 3 (N3) as the main parameter, which were lnk = -1.98 - 0.19 N3 for the water/N-SiO2 system and lnk = -1.56 - 0.34 N3 for the air/N-SiO2 system, with the correlation coefficient (R2) of 0.66 and 0.73, leave-one-out cross-validation (Q2LOO) of 0.51 and 0.59, respectively, and bootstrapping validation coefficients (Q2BOOT) values of both 0.74, confirming that the models were well fitted and showed high robustness and prediction ability. This study provides valuable insights into photocatalytic degradation studies of PCBs.
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Natural product structures have long provided valuable pharmacophores and even candidates for drug discovery. Tanshinone scaffold showed moderately inhibitory activity in NLRP3 inflammasome/IL-1ß pathway. Herein, we designed a series of derivatives on different regions of Tanshinone IIA (TNA) scaffold. The biological evaluation identified compound T10, a scaffold hybrid of TNA and salicylic acid, as a potent NLRP3 inflammasome inhibitor. Mechanistically, T10 inhibits the production of ROS and prevents NLRP3 inflammasome-dependent IL-1ß production. In addition, treatment with T10 significantly attenuated inflammatory response in DSS-induced peritonitis. Our work describes a potential tanshinone-based derivative, which needs to be further structurally optimized as NLRP3 inflammasome inhibitors for treating inflammatory disorders.
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Abietanos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Abietanos/síntese química , Abietanos/química , Abietanos/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Desenho de Fármacos , Linhagem Celular Tumoral , Animais , CamundongosRESUMO
Considering that waste incineration fly ash is the main carrier of dioxins and can migrate over long distances in the atmosphere, it is of great significance to study the photochemical transformation behavior of dioxins on the surface of fly ash. In this work, 2-chlorodibenzo-p-dioxin (2-CDD) was selected to conduct a systematic photochemical study. The influence of various factors on the photodegradation of 2-CDD were first explored, and the results showed that small particle size of fly ash, low concentration of 2-CDD and appropriate level of humidity were more conducive to photodegradation, with the highest degradation percentage reaching 76%-84%. The components of fly ash (Zn (â ¡), Al (â ¢), Cu (â ¡) and SiO2) also had a certain promoting effect on the degradation of 2-CDD, which increases the degradation efficiency by 10%-20%, because they could act as effective photocatalysts to produce free radicals for reaction. With a higher total light exposure intensity, natural light environments led to a more complete degradation of 2-CDD than laboratory Xe lamp irradiation (90% degradation Vs. 79% degradation). Based on chemical probe and radical quenching experiment, hydroxyl radical also contributed to 2-CDD photodegradation on fly ash. A total of 16 intermediate products were detected by mass spectrometry analysis, and four initial reaction pathways of 2-CDD were speculated in the process, including dechlorination, ether bond cleavage, hydroxyl substitution, and hydroxyl addition. According to the results of density functional theory calculation, the reaction channels of ether bond cleavage and â¢OH attack were determined. The toxicity assessment software tool (TEST) was used to assess the toxicity and bioconcentration coefficient of reaction products, and it was found that the overall toxicity of the photodegradation products was reduced. This study would provide new insights into the environmental fate of dioxins during long-range atmospheric migration process.
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Dioxinas , Metais Pesados , Eliminação de Resíduos , Resíduos Sólidos/análise , Dioxinas/análise , Cinza de Carvão/análise , Fotólise , Dióxido de Silício , Incineração/métodos , Éteres , Eliminação de Resíduos/métodos , Carbono/química , Metais Pesados/análiseRESUMO
Bacteriophages can help the treatment of bacterial infections yet require in-silico models to deal with the great genetic diversity between phages and bacteria. Despite the tolerable prediction performance, the application scope of current approaches is limited to the prediction at the species level, which cannot accurately predict the relationship of phages across strain mutants. This has hindered the development of phage therapeutics based on the prediction of phage-bacteria relationships. In this paper, we present, PB-LKS, to predict the phage-bacteria interaction based on local K-mer strategy with higher performance and wider applicability. The utility of PB-LKS is rigorously validated through (i) large-scale historical screening, (ii) case study at the class level and (iii) in vitro simulation of bacterial antiphage resistance at the strain mutant level. The PB-LKS approach could outperform the current state-of-the-art methods and illustrate potential clinical utility in pre-optimized phage therapy design.
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Infecções Bacterianas , Bacteriófagos , Humanos , Bacteriófagos/genética , Bactérias/genéticaRESUMO
BACKGROUND: The obesity rate of adolescents is gradually increasing, which seriously affects their mental health, and sleep plays an important role in adolescent obesity. AIM: To investigate the relationship between sleep rhythm and obesity among adolescents and further explores the interactive effect of sleep rhythm and gender on adolescent obesity, providing a theoretical basis for developing interventions for adolescent obesity. METHODS: Research data source Tianjin Mental Health Promotion Program for Students. From April to June 2022, this study selected 14201 students from 13 middle schools in a certain district of Tianjin as the research subject using the convenient cluster sampling method. Among these students, 13374 accepted and completed the survey, with an effective rate of 94.2%.The demographic data and basic information of adolescents, such as height and weight, were collected through a general situation questionnaire. The sleep rhythm of adolescents was evaluated using the reduced version of the morningness-eveningness questionnaire. RESULTS: A total of 13374 participants (6629 females, accounting for 49.56%; the average age is 15.21 ± 1.433 years) were analyzed. Among them, the survey showed that 2942 adolescent were obesity, accounting for 22% and 2104 adolescent were overweight, accounting for 15.7%. Among them, 1692 male adolescents are obese, with an obesity rate of 25.1%, higher than 18.9% of female adolescents. There is a statistically significant difference between the three groups (χ2 = 231.522, P < 0.000). The obesity group has the smallest age (14.94 ± 1.442 years), and there is a statistical difference in age among the three groups (F = 69.996, P < 0.000).Obesity rates are higher among individuals who are not-only-child, have residential experience within six months, have family economic poverty, and have evening-type sleep (P < 0.05). Logistic regression analysis shows a correlation between sleep rhythm and adolescent obesity. Evening-type sleep rhythm can increase the risk of obesity in male adolescents [1.250 (1.067-1.468)], but the effect on female obesity is not remarkable. Further logistic regression analysis in the overall population demonstrates that the interaction between evening-type sleep rhythm and the male gender poses a risk of adolescent obesity [1.122 (1.043-1.208)]. CONCLUSION: Among adolescents, the incidence of obesity in males is higher than in females. Evening-type sleep rhythm plays an important role in male obesity but has no significant effect on female obesity. Progressive analysis suggests an interactive effect of sleep rhythm and gender on adolescent obesity, and the combination of evening-type sleep and the male gender promotes the development of adolescent obesity. In formulating precautions against adolescent obesity, obesity in male adolescents with evening-type sleep should be a critical concern.
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In this work, the removal and transformation process of diethyl phthalate (DEP) in UV/dichloroisocyanurate (UV/DCCNa) and UV/sodium hypochlorite (UV/NaClO) systems were compared to evaluate the application potential of UV/DCCNa technology. Compared with UV/NaClO, UV/DCCNa process has the advantage of DEP removal and caused a higher degradation efficiency (93.8%) within 45 min of oxidation in ultrapure water due to the sustained release of hypochloric acid (HOCl). Fourteen intermediate products were found by high-resolution mass spectrometry, and the transformation patterns including hydroxylation, hydrolysis, chlorination, cross-coupling, and nitrosation were proposed. The oxidation processes were also performed under quasi-realistic environmental conditions, and it was found that DEP could be effectively removed in both systems, with yields of disinfection byproduct meeting the drinking water disinfection standard (<60.0 µg/L). Comparing the single system, the removal of DEP decreased in the mixed system containing five kinds of PAEs, which could be attributed to the regeneration of DEP and the competitive effect of â¢OH occurred among the Dimethyl phthalate (DMP), DEP, Dipropyl phthalate (DPrP), Diallyl phthalate (DAP) and Diisobutyl phthalate (DiBP). However, a greater removal performance presented in UV/DCCNa system compared with UV/NaClO system (69.4% > 62.1%). Further, assessment of mutagenicity and developmental toxicity by Toxicity Estimation Software Tool (T.E.S.T) software indicated that UV/DCCNa process has fewer adverse effects on the environment and is a more environmentally friendly chlorination method. This study may provide some guidance for selecting the suitable disinfection technology for drinking water treatment.
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Água Potável , Ácidos Ftálicos , Poluentes Químicos da Água , Purificação da Água , Água Potável/análise , Poluentes Químicos da Água/análise , Ácidos Ftálicos/toxicidade , Oxirredução , Purificação da Água/métodosRESUMO
The emergence of antibiotic-resistant bacteria (ARB) caused by the overuse of antibiotics severely threatens human health. Hospital sewage may be a key transmission hub for ARB. However, the complex link between the microbiome and resistomeresistance in hospital sewage remains unclear. In this study, metagenomic assembly and binning methods were used to investigate the microbial community, resistome, and association of antibiotic resistance genes (ARGs) with ARB in sewage from 10 representative sites (outpatient building, surgery building, internal medicine buildings [IMB1-4], staff dormitory, laboratory animal building, tuberculosis building [TBB], and hospital wastewater treatment plant) of a hospital in Shanghai from June 2021 to February 2022. A total of 252 ARG subtypes, belonging to 17 antibiotic classes, were identified. The relative abundance of KPC-2 was higher at IMBs and TBB than at other sites. Of the ARG-carrying contigs, 47.3%-62.6% were associated with mobile genetic elements, and the proportion of plasmid-associated ARGs was significantly higher than that of chromosome-associated ARGs. Although a similar microbiome composition was shared, certain bacteria were enriched at different sites. Potential pathogens Enterococcus B faecium and Klebsiella pneumoniae were primarily enriched in IMB2 and IMB4, respectively. The same ARGs were identified in diverse bacterial hosts (especially pathogenic bacteria), and accordingly, the latter possessed multiple ARGs. Furthermore, gene flow was frequently observed in the sewage of different buildings. The results provide crucial information on the characterization profiles of resistomes in hospital sewage in Shanghai.IMPORTANCEEnvironmental antibiotic resistance genes (ARGs) play a critical role in the emergence and spread of antimicrobial resistance, which poses a global health threat. Wastewater from healthcare facilities serves as a significant reservoir for ARGs. Here, we characterized the microbial community along with the resistome (comprising all antibiotic resistance genes) in wastewater from a specialized hospital for infectious diseases in Shanghai. Potential pathogenic bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus B faecium) were frequently detected in hospital wastewater and carried multiple ARGs. A complex link between microbiome and resistome was observed in the wastewater of this hospital. The monitoring of ARGs and antibiotic-resistant bacteria (ARB) in hospital wastewater might be of great significance for preventing the spread of ARB.
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Doenças Transmissíveis , Microbiota , Animais , Humanos , Esgotos/microbiologia , Águas Residuárias , Genes Bacterianos , Antibacterianos , Antagonistas de Receptores de Angiotensina , China , Inibidores da Enzima Conversora de Angiotensina , Bactérias/genética , Doenças Transmissíveis/genética , HospitaisRESUMO
Bisphenol B (BPB, 2,2-bis(4-hydroxyphenyl) butane), as a substitute for bisphenol A, has been widely detected in the environment and become a potential threat to environmental health. This work found that silver oxide nanoparticles (Ag2O) could greatly promote the removal of BPB by ferrate (Fe(VI)). With the presence of 463 mg/L Ag2O, the amount of Fe(VI) required for the complete removal of 10 µM BPB will be reduced by 70%. Meanwhile, the recyclability and stability of Ag2O have been verified by recycling experiments. The characterization results and in situ electrochemical analyses showed that Ag(II) was produced from Ag(I) in the Fe(VI)-Ag2O system, which has a higher electrode potential to oxidize BPB to enhance its removal. A total of 13 intermediates were identified by high-resolution mass spectrometry, and three main reaction pathways were proposed, including oxygen transfer, bond breaking, and polymerization. Based on the toxicity assessment through the ECOSAR program, it is considered that the presence of Ag2O reduced the toxicity of BPB oxidation intermediates to aquatic organisms. These results would deepen our understanding of the interaction between Fe(VI) and Ag2O, which may provide an efficient and environmentally friendly method for water and wastewater treatment.
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Nanopartículas , Poluentes Químicos da Água , Purificação da Água , Ferro/química , Oxirredução , Poluentes Químicos da Água/toxicidade , Purificação da Água/métodosRESUMO
Phage therapy, a century-long treatment targeting bacterial infection, was widely abandoned after the clinical availability of antibiotics in the mid-20th century. However, the crisis of antimicrobial resistance today led to its revival in many countries. While many articles dive into its clinical application now, little research is presenting phage therapy from a regulatory perspective. Here, we focus on the regulations of phage therapy by dividing sections into Eastern Europe where it was never abandoned and Western Europe, Australia, the United States, India, and China where it only re-attracted researchers' attention in recent decades. New insights about its regulations in China are provided as little English literature has specifically discussed this previously. Ultimately, by introducing the regulations in phage therapy for human health across representative countries, we hope to provide ideas of how countries may borrow each other's adapting legislation in phage therapy to best overcome the current regulatory hurdles.
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Cobalt nickel bimetallic oxides (NiCo2O4) have received numerous attentions in terms of their controllable morphology, high temperature, corrosion resistance and strong electromagnetic wave (EMW) absorption capability. However, broadening the absorption bandwidth is still a huge challenge for NiCo2O4-based absorbers. Herein, the unique NiCo2O4@C core-shell microcubes with hollow structures were fabricated via a facile sacrificial template strategy. The concentration of oxygen vacancies and morphologies of the three-dimensional (3D) cubic hollow core-shell NiCo2O4@C framework were effectively optimized by adjusting the calcination temperature. The specially designed 3D framework structure facilitated the multiple reflections of incident electromagnetic waves and provided rich interfaces between multiple components, generating significant interfacial polarization losses. Dipole polarizations induced by oxygen vacancies could further enhance the attenuation ability for the incident EM waves. The optimized NiCo2O4@C hollow microcubes exhibit superior EMW absorption capability with minimum RL (RLmin) of -84.45 dB at 8.4 GHz for the thickness of 3.0 mm. Moreover, ultrabroad effective absorption bandwidth (EAB) as large as 12.48 GHz (5.52-18 GHz) is obtained. This work is believed to illuminate the path to synthesis of high-performance cobalt nickel bimetallic oxides for EMW absorbers with excellent EMW absorption capability, especially in broadening effective absorption bandwidth.
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This work was to investigate the transformation of coexisting decabromodiphenyl ether (BDE-209) on microplastics and their possible interactions in UV/chlorine process. Compared with pristine microplastics, the highly aged polystyrene (PS) showed an inhibitory effect on degradation of BDE-209. Increasing initial concentration of BDE-209 on PS inhibited degradation, while the chlorine concentration and pH did not affect the final degradation efficiency. Moreover, the presence of NO3-, SO42-, HCO3- and HA in water was unfavorable for BDE-209 degradation. According to the experimental and calculation results, the contribution to the degradation of BDE-209 was ranked as direct photolysis > HO⢠> â¢Cl in the UV/ chlorine system. Chlorination products released by PS during UV/chlorination were detected. Four possible reaction pathways of BDE-209 were proposed, which mainly involved debromination, hydroxylation, chlorine substitution, cleavage of ether bond, and intramolecular elimination of HBr. It was worth noting that PS microplastics not only inhibited the degradation of BDE-209, but also affected the type and abundance of its transformation products. Meanwhile, interaction products of PS and BDE-209 were determined, which was attributed to reactions of PS-derived radicals with â¢Br/â¢C6Br5 and â¢Cl. Results of toxicity evaluation showed that the introduction of carbon-halogen bonds, especially C-Br bond, increased the toxicity of chain scission products of PS. This work provides some new insights into transformation, interaction, and associated ecological risks of coexisting microplastics and surface adsorbed contaminants in the UV/chlorine process of drinking water treatment plants (DWTPs) and wastewater treatment plants (WWTPs).
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OBJECTIVES: Phage-resistant bacteria often emerge rapidly when performing phage therapy. However, the relationship between the emergence of phage-resistant bacteria and improvements in clinical symptoms is still poorly understood. METHODS: An inpatient developed a pulmonary infection caused by multidrug-resistant Klebsiella pneumoniae. He received a first course of treatment with a single nebulized phage (ΦKp_GWPB35) targeted at his bacterial isolate of Kp7450. After 14 days, he received a second course of treatment with a phage cocktail (ΦKp_GWPB35+ΦKp_GWPA139). Antibiotic treatment was continued throughout the course of phage therapy. Whole-genome analysis was used to identify mutations in phage-resistant strains. Mutated genes associated with resistance were further analysed by generating knockouts of Kp7450 and by measuring phage adsorption rates of bacteria treated with proteinase K and periodate. Bacterial virulence was evaluated in mouse and zebrafish infection models. RESULTS: Phage-resistant Klebsiella pneumoniae strains emerged after the second phage treatment. Comparative genomic analyses revealed that fabF was deleted in phage-resistant strains. The fabF knockout strain (Kp7450ΔfabF) resulted in an altered structure of lipopolysaccharide (LPS), which was identified as the host receptor for the therapeutic phages. Virulence evaluations in mice and zebrafish models showed that LPS was the main determinant of virulence in Kp7450 and alteration of LPS structure in Kp7450ΔfabF, and the bacteriophage-resistant strains reduced their virulence at cost. DISCUSSION: This study may shed light on the mechanism by which some patients experience clinical improvement in their symptoms post phage therapy, despite the incomplete elimination of pathogenic bacteria.
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Bacteriófagos , Infecções por Klebsiella , Terapia por Fagos , Humanos , Masculino , Animais , Camundongos , Klebsiella pneumoniae/genética , Virulência , Peixe-Zebra , Infecções por Klebsiella/microbiologia , Bacteriófagos/genética , Terapia por Fagos/métodos , Lipopolissacarídeos , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
The genus Houpoea belongs to the family Magnoliaceae, and the species in this genus have important medicinal values. However, the investigation of the correlation between the evolution of the genus and its phylogeny has been severely hampered by the unknown range of species within the genus and the paucity of research on its chloroplast genome. Thus, we selected three species of Houpoea: Houpoea officinalis var officinalis (OO), Houpoea officinalis var. biloba (OB), and Houpoea rostrata (R). With lengths of 160,153 bp (OO), 160,011 bp (OB), and 160,070 bp (R), respectively, the whole chloroplast genomes (CPGs) of these three Houpoea plants were acquired via Illumina sequencing technology, and the findings were annotated and evaluated. These three chloroplast genomes were revealed by the annotation findings to be typical tetrads. A total of 131, 132, and 120 different genes were annotated. The CPGs of the three species had 52, 47, and 56 repeat sequences, which were primarily found in the ycf2 gene. A useful tool for identifying species is the approximately 170 simple sequence repeats (SSRs) that have been found. The border area of the reverse repetition region (IR) was studied, and it was shown that across the three Houpoea plants, it is highly conservative, with only changes between H. rostrata and the other two plants observed. Numerous highly variable areas (rps3-rps19, rpl32-trnL, ycf1, ccsA, etc.) have the potential to serve as the barcode label for Houpoea, according to an examination of mVISTA and nucleotide diversity (Pi). Phylogenetic relation indicates that Houpoea is a monophyletic taxon, and its genus range and systematic position are consistent with the Magnoliaceae system of Sima Yongkang-Lu Shugang, including five species and varieties of H. officinalis var. officinalis, H. rostrata, H. officinalis var. biloba, Houpoea obovate, and Houpoea tripetala, which evolved and differentiated from the ancestors of Houpoea to the present Houpoea in the above order. This study provides valuable information on the genus Houpoea, enriches the CPG information on Houpoea genus, and provides genetic resources for the further classification of and phylogenetic research on Houpoea.
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Genoma de Cloroplastos , Magnolia , Filogenia , Genoma de Cloroplastos/genética , Magnolia/genética , Sequências Repetitivas de Ácido NucleicoRESUMO
Benzophenones (BPs) are commonly used as UV filters in cosmetics and plastics products and are potentially toxic to the environment. This paper presents kinetics and products of BPs oxidation by ferrate(VI) (FeO42-, Fe(VI)) promoted by permanganate (Mn(VII)) . Degradation of 10.0 µM 2,2'-dihydroxy-4-methoxybenzophenone (BP-8)were determined under different experimental conditions ([Mn(VII)] = 0.5-1.5 µM, [Fe(VI)] = 50-150 µM, and pH = 7.0-10.0). The addition of Mn(VII) traces to Fe(VI)-BP-8 solution enhanced kinetics and efficiency of the removal. Similar enhanced removals were also seen for other BPs (BP-1, BP-3, and BP-4) under optimized conditions. The second-order rate constants (k, M-1s-1) of the degradation of BPs showed positive relationship with the energy of the highest occupied orbital (EHOMO). The possible interaction between Mn(VII) and BP-8 and the enhanced generation of Fe(V)/Fe(IV) and â¢OH was proposed to facilitate the oxidation of the target benzophenone, supported by in-situ electrochemical measurements, theoretical calculations and reactive species quenching experiments. Thirteen oxidation products of BP-8 suggested hydroxylation, bond breaking, polymerization and carboxylation steps in the oxidation. Toxicity assessments by ECOSAR program showed that the oxidized intermediate products posed a tapering ecological risk during the degradation process. Overall, the addition of Mn(VII) could improve the oxidation efficiency of Fe(VI).
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Manganês , Poluentes Químicos da Água , Manganês/química , Poluentes Químicos da Água/química , Oxirredução , Benzofenonas , CinéticaRESUMO
The rise of antimicrobial resistance (AMR) is a major global public health concern, and it is urgent to develop new antimicrobial drugs and alternative therapies. There has been growing interest in the use of phage therapy as an alternative to treat AMR, and it has shown promising results in early studies and clinical trials. Phage quantification is a crucial step in the development and application of phage therapy. The traditional double-layer plaque assay requires cumbersome manual operations and typically takes up to 18 h to yield a rough phage estimation. Spectrophotometry, flow cytometry, and PCR-based methods cannot distinguish between infectious and noninfectious phages. Here, we developed a digital biosensing method for rapid bacteriophage quantification on a digital phage SlipChip (dp-SlipChip) microfluidic device containing 2304 microdroplets in 3 nL. By compartmentalizing the phages and bacteria in nanoliter droplets and analyzing the growth profile of bacteria at 3 h, the number of infectious phages can be precisely quantified. The results from the dp-SlipChip were consistent with the traditional double-layer plaque assay method and exhibited higher consistency and repeatability. The dp-SlipChip does not require a complex fluidic handling instrument to generate and manipulate droplets. This SlipChip-based digital biosensing method not only provides a promising tool for rapid phage quantification, which is important for the use of phages in clinical practice to treat antimicrobial-resistant bacteria, but can also be used as an ultrasensitive, high-specificity method to detect bacteria. Furthermore, this approach can be applied to other digital biology studies that require analysis at the single-object level.