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1.
Environ Pollut ; 320: 121076, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36641065

RESUMO

Microplastic pollution threatens water systems worldwide. As one of the most important parts of city wastewater treatment, wastewater treatment plants are not only microplastics interception barriers but also emission sources. Water samples were collected from each sewage treatment plant stage and sludge from the sludge dewatering room. Microplastics were extracted using wet peroxide oxidation and flotation, and the abundance, size, shape, and polymer type of microplastics were detected. Basis on the results, the influence of each process on the removal rate and characteristics of microplastics under the same influent source was analysed. The influent microplastic concentration in this study was 32.5 ± 1.0 n/L, which rapidly decreased after treatment. The removal rates of the sequencing batch reactor activated sludge, cyclic activated sludge, and anaerobic anoxic oxic technologies were 73.0%, 75.6%, and 83.9%, respectively. Most microplastics were transported to the sludge, and the concentration of microplastics in dehydrated sludge was 27.2 ± 3.1 n/g. Microplastics removal occurred primarily during the primary and secondary stages. Disposal processes, settling time, and process design affected wastewater treatment plant microplastic removal rates at each stage. Significant differences in microplastic characteristics were observed at each stage, with the most abundant being fragment shaped, particle sizes of 30-100 µm, and black in colour. Sixteen polymer types were identified using a Raman spectrometer. The predominant polymers are polypropylene, polyethylene, and polyethylene terephthalate. This study demonstrates that optimising the process design of existing wastewater treatment plants is crucial for the prevention and control of microplastic pollution. It is suggested that the process settings of contemporary wastewater treatment plants should be studied in depth to develop a scientific foundation for avoiding and managing microplastic pollution in urban areas.

2.
Anal Methods ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36606802

RESUMO

Plasma renin activity (PRA) is recommended as the first screening indicator for primary aldosteronism. Immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed for quantifying PRA, but the interchangeability across assays and laboratories was suboptimal, which predominantly related to the differences in the plasma incubation strategy. This study aims to establish and validate a designed comparison method based on LC-MS/MS. The sensitivity, matrix effect, precision, accuracy, and storage stability were validated according to the Clinical Laboratory Standard Institution (CLSI) C-62A guidelines. The plasma incubation procedure was optimized to achieve maximum PRA results. The short-term stability of PRA plasma was assessed at 4 °C and room temperature (RT) for specific time points. Differences from the baseline were calculated using a one-way analysis of variance. The designed comparison method for PRA measurement exhibits excellent performance characteristics. The results from the 2022 national external quality assessment scheme for PRA showed good consistency of the developed method with other LC-MS/MS methods (relative biases: -6.8% to 4.6%), which demonstrated the reliability of the established method. Two sets of generation buffers were optimized to maximize the renin activity. The acetate buffer was recommended to be used in laboratory practice due to better metrological sensitivity. PRA plasma is stable for one day at 4 °C and RT. In summary, a reliable, traceable, and reproducible LC-MS/MS method for determining PRA was well-established and validated. The recommended incubation protocol is hoped to reduce the discrepancy in Ang1 generation. The evaluated short-term stability for PRA plasma could provide flexibility in clinical practice.

3.
Microsyst Nanoeng ; 9: 3, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36597510

RESUMO

The COVID-19 pandemic has posed enormous challenges for existing diagnostic tools to detect and monitor pathogens. Therefore, there is a need to develop point-of-care (POC) devices to perform fast, accurate, and accessible diagnostic methods to detect infections and monitor immune responses. Devices most amenable to miniaturization and suitable for POC applications are biosensors based on electrochemical detection. We have developed an impedimetric immunosensor based on an interdigitated microelectrode array (IMA) to detect and monitor SARS-CoV-2 antibodies in human serum. Conjugation chemistry was applied to functionalize and covalently immobilize the spike protein (S-protein) of SARS-CoV-2 on the surface of the IMA to serve as the recognition layer and specifically bind anti-spike antibodies. Antibodies bound to the S-proteins in the recognition layer result in an increase in capacitance and a consequent change in the impedance of the system. The impedimetric immunosensor is label-free and uses non-Faradaic impedance with low nonperturbing AC voltage for detection. The sensitivity of a capacitive immunosensor can be enhanced by simply tuning the ionic strength of the sample solution. The device exhibits an LOD of 0.4 BAU/ml, as determined from the standard curve using WHO IS for anti-SARS-CoV-2 immunoglobulins; this LOD is similar to the corresponding LODs reported for all validated and established commercial assays, which range from 0.41 to 4.81 BAU/ml. The proof-of-concept biosensor has been demonstrated to detect anti-spike antibodies in sera from patients infected with COVID-19 within 1 h. Photolithographically microfabricated interdigitated microelectrode array sensor chips & label-free impedimetric detection of COVID-19 antibody.

4.
Phys Chem Chem Phys ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36644907

RESUMO

The sustainable rise in global warming and the consumption of fossil fuels considerably contribute to energy and environmental issues. To address these issues, semiconductor heterostructures can be used to generate clean energy sources as alternative energy sources and to reduce environmental impacts. Herein, we report the synthesis of a ternary semiconductor of the CdS/WO3/g-C3N4 (i.e. C-CNW) nanostructured composite for hydrogen production and dye degradation under visible-light irradiation. The structural properties of the prepared materials were studied using a series of investigational analyses. The 3C-CNW nanostructure photocatalyst exhibited faster malachite green (MG) dye photodegradation within 105 min and the highest hydrogen production rate is 868.23 µmol g-1 h-1 under visible light illumination. Moreover, the photocatalytic hydrogen production of the 3C-CNW nanostructure photocatalyst with various scavengers was analyzed. Its higher photocatalytic activity is ascribed to the Z-scheme mechanism, which induces rapid diffusion of photoinduced charges within the ternary photocatalyst with its optical bandgap. This proposed strategy is useful to improve photocatalysts that play a role in mitigating energy and environmental issues.

5.
Angew Chem Int Ed Engl ; : e202216837, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36598399

RESUMO

Developing efficient and stable transition metal oxides catalysts for energy conversion processes such as oxygen evolution reaction and oxygen reduction reaction is one of the key measures to solve the problem of energy shortage. The spin state of transition metal oxides is strongly correlated with their catalytic activities. In an octahedral structure of transition metal oxides, the spin state of active centers could be regulated by adjusting the splitting energy and the electron pairing energy. Regulating spin state of active centers could directly modulate the d orbitals occupancy, which influence the strength of metal-ligand bonds and the adsorption behavior of the intermediates. In this review, we clarified the significance of regulating spin state of the active centers. Subsequently, we discussed several characterization technologies for spin state and some recent strategies to regulate the spin state of the active centers. Finally, we put forward some views on the future research direction of this vital field.

6.
Nat Commun ; 14(1): 138, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627283

RESUMO

ß-Nucleosides and their analogs are dominant clinically-used antiviral and antitumor drugs. α-Nucleosides, the anomers of ß-nucleosides, exist in nature and have significant potential as drugs or drug carriers. Currently, the most widely used methods for synthesizing ß- and α-nucleosides are via N-glycosylation and pentose aminooxazoline, respectively. However, the stereoselectivities of both methods highly depend on the assisting group at the C2' position. Herein, we report an additive-controlled stereodivergent iodocyclization method for the selective synthesis of α- or ß-nucleosides. The stereoselectivity at the anomeric carbon is controlled by the additive (NaI for ß-nucleosides; PPh3S for α-nucleosides). A series of ß- and α-nucleosides are prepared in high yields (up to 95%) and stereoselectivities (ß:α up to 66:1, α:ß up to 70:1). Notably, the introduced iodine at the C2' position of the nucleoside is readily functionalized, leading to multiple structurally diverse nucleoside analogs, including stavudine, an FDA-approved anti-HIV agent, and molnupiravir, an FDA-approved anti-SARS-CoV-2 agent.


Assuntos
Fármacos Anti-HIV , COVID-19 , Humanos , Nucleosídeos , Estereoisomerismo , Antivirais/farmacologia
7.
Int J Ophthalmol ; 16(1): 22-32, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36659954

RESUMO

AIM: To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy (PVR) and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma. METHODS: Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus, followed by treatment with a slow-release dexamethasone implant (Ozurdex) or sham injection. Left eyes were used as normal controls. The intraocular pressure (IOP) was monitored using an iCare tonometer. PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk; specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction, Western blot, protein chip analysis, or immunofluorescence staining. RESULTS: During the observation period, PVR severity gradually increased. Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group. Ozurdex significantly alleviated PVR development and Müller cell gliosis. Post-traumatic inflammation fluctuated and was persistent. The interleukin-1ß (IL-1ß) mRNA level was significantly upregulated, peaking on day 3 and increasing again on day 21 after injury. The expression of nod-like receptor family pyrin domain containing 3 (NLRP3) showed a similar trend that began earlier than that of IL-1ß expression. Ozurdex suppressed the expression of IL-1ß, NLRP3, and phosphorylated nuclear factor-kappa B (NF-κB). The average IOP after treatment was within normal limits. CONCLUSION: The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk. Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis, and thus alleviates PVR severity. This study highlights the important role of IL-1ß, and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1ß inflammatory axis. In summary, Ozurdex provides a potential therapeutic option for traumatic PVR.

8.
ESC Heart Fail ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36669759

RESUMO

Reports on the treatment of nonobstructive hypertrophic cardiomyopathy (HCM) and severe mitral valve regurgitation (MR) with transcatheter edge-to-edge repair (TEER) are rare. Herein, we present the case of a 68-year-old Chinese man with nonobstructive HCM admitted to our hospital with dyspnoea [New York Heart Association (NYHA) functional Class IV]. Transthoracic echocardiography indicated severe MR in addition to asymmetric hypertrophy of the left ventricle. Despite administering maximal medical therapy for heart failure, the symptoms were not alleviated; because of the high risk of open surgery, TEER was performed for MR. After 4 months of follow-up, the patient showed a significant improvement in symptoms. Herein, we also discuss and review the pathophysiology and treatment strategies for HCM patients with heart failure.

9.
Chem Asian J ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36647683

RESUMO

Dinitrogen (N2) activation is particularly challenging under ambient conditions because of its large highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap (10.8 eV) and high bond dissociation energy (945 kJ mol-1) of the NΞN triple bond, attracting considerable attention from both experimental and theoretical chemists. However, most effort has focused on metallic systems. In contrast, nitrogen activation by frustrated Lewis pairs (FLPs) has been initiated recently via theoretical calculations. Here we perform density functional theory (DFT) calculations to screen a series of experimentally viable FLPs for small-molecule activation including N2, O2, CO, CO2, CS2, H2O and CH4. In addition, aromaticity is found to play an important role in most of these small-molecule activation. The particularly thermodynamic stabilities of the activation products and low reaction barriers could be a step forward for the development of FLP towards small-molecule activation including N2, inviting experimental chemists' verification.

10.
Environ Res ; 220: 115235, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36621549

RESUMO

The tanglesome allocation of landscape types at various spatial dimensions is an important component influencing the quality of groundwater environment in karst cities. Trace elements can be used as indicators of the extent of impact on groundwater which is an effective means of tracing groundwater contamination. In this study, we studied the influence of landscape patterns on trace elements in groundwater of typical karst cities in Southwest China (Guiyang City) on a multi-spatial scale by using multivariate statistical analysis. According to the sampling points, buffer zone scales with different radii (500 m, 1000 m, 1500 m, and 4000 m) were established to quantify the land use model. There are suburban and urban differences in trace element content. The city center has higher levels of trace elements compared to suburban areas, especially Li, Ni, Tl, Cu, Sr, Co, As, and Mn. In addition, the outcomes of the multiple linear regression had shown that the size effect of the association from landscape pattern to trace elements varies with different indicators and parameters. The results of redundancy analysis showed an overall change in trace elements was better interpreted by the landscape pattern of the 1500 m-scale buffer. At the same time, at the 1500 m scale, Ni, Tl, Cu, Co, As, Cr, Sr, Li, and Mn were positively correlated with the urban landscape index (4LPI, 4LSI), influenced by urban anthropogenic activities, while Cd, Zn, and Pb were positively correlated with the cropland landscape index (1AI, 1LPI), influenced by agricultural activities. This study indicates that trace elements are a reliable indicator for tracing groundwater contamination. The buffer zone can reflect the extent of urban impacts on groundwater and provide a new and effective analytical tool for groundwater management.

11.
Nat Commun ; 14(1): 340, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670129

RESUMO

Renewable electricity-powered CO evolution from CO2 emissions is a promising first step in the sustainable production of commodity chemicals, but performing electrochemical CO2 reduction economically at scale is challenging since only noble metals, for example, gold and silver, have shown high performance for CO2-to-CO. Cu is a potential catalyst to achieve CO2 reduction to CO at the industrial scale, but the C-C coupling process on Cu significantly depletes CO* intermediates, thus limiting the CO evolution rate and producing many hydrocarbon and oxygenate mixtures. Herein, we tune the CO selectivity of Cu by alloying a second metal Sb into Cu, and report an antimony-copper single-atom alloy catalyst (Sb1Cu) of isolated Sb-Cu interfaces that catalyzes the efficient conversion of CO2-to-CO with a Faradaic efficiency over 95%. The partial current density reaches 452 mA cm-2 with approximately 91% CO Faradaic efficiency, and negligible C2+ products are observed. In situ spectroscopic measurements and theoretical simulations reason that the atomic Sb-Cu interface in Cu promotes CO2 adsorption/activation and weakens the binding strength of CO*, which ends up with enhanced CO selectivity and production rates.

12.
Ecotoxicol Environ Saf ; 249: 114424, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36525945

RESUMO

Hydrogeochemical processes of trace elements (TEs) are of considerable significance to river water and groundwater resource assessment and utilization in the karst region. Therefore, seven TEs were analyzed to investigate their contents, spatial variations, sources, and controlling factors in Guiyang, a typical karst urban area in southwest China. The results showed that the average content of TEs in river water (e.g., As = 1.44 ± 0.47 µg/L andCo = 0.15 ± 0.06 µg/L) was higher than that of groundwater (e.g., As = 0.51 ± 0.42 µg/L andCo = 0.09 ± 0.05 µg/L). The types of groundwater samples were dominated by Ca/Mg-HCO3 and Ca/Mg-Cl types, while those of the river water samples were Ca-Cl and Ca/Mg-Cl types. Principal component analysis (PCA) and correlation analysis (CA) analyses indicated that As and Mn in the groundwater of the study area were related to river infiltration. The end-member analysis further revealed that river infiltration (As = 0.86-1.81 µg/L, Cl/SO42- = 0.62-0.89) and urban activities (As = 0.21-0.32 µg/L, Cl/SO42- = 0.51-0.89) were two main controlling factors of TEs (e.g., As, Co, and Mn) in the study area. In addition, the ion ratios in river and groundwater samples indicated that the weathering of carbonates was also an important control on the hydrogeochemistry of TEs (e.g., Fe and Mn) in Guiyang waters. This study showed that the trace element (TE) contents of groundwater in the Guiyang area were greatly associated with urban input and river recharge, and provided a new perspective for understanding the geochemical behavior of TEs in urban surface and groundwater bodies, which will help the protection of groundwater in the karst areas of southwest China.


Assuntos
Água Subterrânea , Oligoelementos , Poluentes Químicos da Água , Rios/química , Oligoelementos/análise , Monitoramento Ambiental , China , Carbonatos/análise , Água Subterrânea/química , Água/análise , Poluentes Químicos da Água/análise
13.
Acad Radiol ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36460582

RESUMO

RATIONALE AND OBJECTIVES: Accurate pretreatment assessment of histological differentiation grade of head and neck squamous cell carcinoma (HNSCC) is crucial for prognosis evaluation. This study aimed to construct and validate a contrast-enhanced computed tomography (CECT)-based deep learning radiomics nomogram (DLRN) to predict histological differentiation grades of HNSCC. MATERIALS AND METHODS: A total of 204 patients with HNSCC who underwent CECT scans were enrolled in this study. The participants recruited from two hospitals were split into a training set (n=124, 74 well/moderately differentiated and 50 poorly differentiated) of patients from one hospital and an external test set of patients from the other hospital (n=80, 49 well/moderately differentiated and 31 poorly differentiated). CECT-based manually-extracted radiomics (MER) features and deep learning (DL) features were extracted and selected. The selected MER features and DL features were then combined to construct a DLRN via multivariate logistic regression. The predictive performance of the DLRN was assessed using ROCs and decision curve analysis (DCA). RESULTS: Three MER features and seven DL features were finally selected. The DLRN incorporating the selected MER and DL features showed good predictive value for the histological differentiation grades of HNSCC (well/moderately differentiated vs. poorly differentiated) in both the training (AUC, 0.878) and test (AUC, 0.822) sets. DCA demonstrated that the DLRN was clinically useful for predicting histological differentiation grades of HNSCC. CONCLUSION: A CECT-based DLRN was constructed to predict histological differentiation grades of HNSCC. The DLRN showed good predictive efficacy and might be useful for prognostic evaluation of patients with HNSCC.

14.
Angew Chem Int Ed Engl ; : e202214259, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36495017

RESUMO

The construction of highly active, durable, and cost-effective catalysts is urgently needed for green hydrogen production. Herein, catalysts consisting of high-density Pt (24 atoms nm-2 ) and Ir (32 atoms nm-2 ) single atoms anchored on Co(OH)2 were constructed by a facile one-step approach. Remarkably, Pt1 /Co(OH)2 and Ir1 /Co(OH)2 only required 4 and 178 mV at 10 mA cm-2 for hydrogen evolution reaction and oxygen evolution reaction, respectively. Moreover, the assembled Pt1 /Co(OH)2 //Ir1 /Co(OH)2 system showed mass activity of 4.9 A mgnoble metal -1 at 2.0 V in an alkaline water electrolyzer, which is 316.1 times higher than that of Pt/C//IrO2 . Mechanistic studies revealed that reconstructed Ir-O6 single atoms and remodeled Pt triple-atom sites enhanced the occupancy of Ir-O bonding orbitals and improved the occupation of Pt-H antibonding orbital, respectively, contributing to the formation of the O-O bond and the desorption of hydrogen. This one-step approach was also generalized to fabricate other 20 single-atom catalysts.

15.
Macromol Biosci ; : e2200453, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36542841

RESUMO

Antisense DNA oligonucleotide (AS) technology is a promising approach to regulate gene expression and cellular processes. For example, ASs can be used to capture the overexpressed, oncogenic miRNAs in tumors to suppress tumor growth. Among many challenges faced by AS approach is the degradation of ASs by nucleases under physiological conditions. Elongating the AS lifespan can substantially enhance the functions of AS. The paper reports a simple strategy to increase the stability of ASs. The authors discover that the ASs degrade quickly if their ends are in unpaired, single-stranded form, but much slower if their ends are in paired duplex form. It is conceivable to integrate this strategy with other strategies (such as chemical modification of ASs backbones) to maximally increase the ASs stabilities.

16.
Gastroenterol Rep (Oxf) ; 10: goac072, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518985

RESUMO

Background: Prognosis varies among stage IV colorectal cancer (CRC). Our study aimed to build a robust prognostic nomogram for predicting overall survival (OS) of patients with stage IV CRC in order to provide evidence for individualized treatment. Method: We collected the information of 16,283 patients with stage IV CRC in the Surveillance, Epidemiology, and End Results (SEER) database and then randomized these patients in a ratio of 7:3 into a training cohort and an internal validation cohort. In addition, 501 patients in the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) database were selected and used as an external validation cohort. Univariate and multivariate Cox analyses were used to screen out significant variables for nomogram establishment. The nomogram model was assessed using time-dependent receiver-operating characteristic curve (time-dependent ROC), concordance index (C-index), calibration curve, and decision curve analysis. Survival curves were plotted using the Kaplan-Meier method. Result: The C-index of the nomogram for OS in the training, internal validation, and external validation cohorts were 0.737, 0.727, and 0.655, respectively. ROC analysis and calibration curves pronounced robust discriminative ability of the model. Further, we divided the patients into a high-risk group and a low-risk group according to the nomogram. Corresponding Kaplan-Meier curves showed that the prediction of the nomogram was consistent with the actual practice. Additionally, model comparisons and decision curve analysis proved that the nomogram for predicting prognosis was significantly superior to the tumor-node-metastasis (TNM) staging system. Conclusions: We constructed a nomogram to predict OS of the stage IV CRC and externally validate its generalization, which was superior to the TNM staging system.

17.
Small ; : e2206878, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539264

RESUMO

Engineering 2D nanosheets with well-defined porous structures and their assembled heterostructure membrane is a promising method to improve osmotic energy conversion. However, it is still a great challenge to directly fabricate 2D nanosheets with regular parallel nanochannels in aqueous media. Here, the desired functional nanosheets and heterostructure membrane device are successfully prepared through a simple interfacial assembly strategy. In this method, monolayer cylindrical monomicelles closely arrange and assemble on the surfaces of graphene oxide, and the resulting nanosheets with monolayered aligned nanowire polymer arrays parallel to the substrate surfaces are then obtained. Subsequently, a heterostructured membrane is constructed by assembling these 2D nanosheets on macroporous alumina. The nanofluidic membrane device with asymmetric geometry and charge polarity exhibits smart ion transport properties, and the output osmotic power density is ≈1.22 and 1.63 times over the reported pure 2D graphene oxide and biomass-derived membranes, respectively. In addition, theoretical calculations are carried out to reveal the mechanisms for ion selectivity and salinity gradient energy conversion. This monolayered interfacial assembly approach can open up new avenues for the synthesis of functional porous low-dimensional nanomaterials and membrane devices, and expand the palette of materials selection for many applications.

18.
Microbiol Spectr ; : e0379022, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36533939

RESUMO

The growing prevalence of antimicrobial resistance poses a grave threat to human health. Among the most difficult bacterial infections to treat are those caused by multidrug-resistant (MDR) Gram-negative pathogens because few effective regimens are available. One approach to this problem is to find ways to increase the activity of old antimicrobials that had seen limited application. Bicyclomycin, an inhibitor of transcription termination, is an example in which the additional inhibition of protein or RNA synthesis increases bicyclomycin-mediated lethality against Gram-negative bacteria. To examine the potential of bicyclomycin for the treatment of MDR bacterial pathogens, we first measured the MICs of bicyclomycin and other widely used antimicrobials against more than 100 multidrug-resistant Gram-negative clinical isolates. Bicyclomycin showed good coverage of carbapenem-resistant Enterobacteriaceae (CRE) and Escherichia coli (MIC50/MIC90 of 25/50 µg/mL for both bacteria) and moderate activity against Klebsiella pneumoniae (MIC50/MIC90 of 50/200 µg/mL). Bicyclomycin also exhibited synergy (e.g., fractional inhibitory concentration [FIC] index of <0.5) with doxycycline for the inhibition of bacterial growth by a checkerboard assay. Although bicyclomycin exhibited very weak lethality by itself, it showed synthetic lethality with doxycycline against K. pneumoniae: the combination killed 100- to 1,000-fold more bacteria than either agent alone. In a murine model of infection, the bicyclomycin-doxycycline combination showed better efficacy than either agent alone, and the combination treatment largely eliminated histopathological manifestations caused by infection. Thus, bicyclomycin, which has largely been limited to the treatment of Gram-negative digestive tract infections, can now be considered for the combination treatment of systemic multidrug-resistant infections caused by CRE, E. coli, and K. pneumoniae. IMPORTANCE As antimicrobial resistance continues to increase, options for effectively treating multidrug-resistant (MDR) Gram-negative infections are declining. Finding ways to enhance the lethality of old agents that have unique molecular targets is important because developing new antimicrobials is becoming increasingly difficult. The present work showed that the old antibiotic bicyclomycin has good bacteriostatic activity against multiple clinical isolates of three significant types of MDR Gram-negative pathogens frequently encountered in hospital infections, as required for the consideration of expanded indications. More significant is the synergistic growth-inhibitory effect and the enhancement of killing by the additional presence of doxycycline since this increases the in vivo efficacy. These data demonstrate that bicyclomycin-containing regimens have potential as new treatment options for MDR Gram-negative infections such as those caused by CRE, E. coli, and K. pneumoniae.

19.
Nutrients ; 14(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36501095

RESUMO

Atherosclerosis (AS) is a chronic inflammatory disease that serves as a common pathogenic underpinning for various cardiovascular diseases. Although high circulating branched-chain amino acid (BCAA) levels may represent a risk factor for AS, it is unclear whether dietary BCAA supplementation causes elevated levels of circulating BCAAs and hence influences AS, and the related mechanisms are not well understood. Here, ApoE-deficient mice (ApoE-/-) were fed a diet supplemented with or without BCAAs to investigate the effects of BCAAs on AS and determine potential related mechanisms. In this study, compared with the high-fat diet (HFD), high-fat diet supplemented with BCAAs (HFB) reduced the atherosclerotic lesion area and caused a significant decrease in serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. BCAA supplementation suppressed the systemic inflammatory response by reducing macrophage infiltration; lowering serum levels of inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6); and suppressing inflammatory related signaling pathways. Furthermore, BCAA supplementation altered the gut bacterial beta diversity and composition, especially reducing harmful bacteria and increasing probiotic bacteria, along with increasing bile acid (BA) excretion. In addition, the levels of total BAs, primary BAs, 12α-hydroxylated bile acids (12α-OH BAs) and non-12α-hydroxylated bile acids (non-12α-OH BAs) in cecal and colonic contents were increased in the HFB group of mice compared with the HFD group. Overall, these data indicate that dietary BCAA supplementation can attenuate atherosclerosis induced by HFD in ApoE-/- mice through improved dyslipidemia and inflammation, mechanisms involving the intestinal microbiota, and promotion of BA excretion.


Assuntos
Aterosclerose , Microbioma Gastrointestinal , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Aminoácidos de Cadeia Ramificada/metabolismo , Aterosclerose/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos e Sais Biliares , Colesterol , Administração Oral , Camundongos Endogâmicos C57BL
20.
Nano Lett ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352348

RESUMO

An efficient catalytic system for nitrogen (N2) photofixation generally consists of light-harvesting units, active sites, and an electron-transfer bridge. In order to track photogenerated electron flow between different functional units, it is highly desired to develop in situ characterization techniques with element-specific capability, surface sensitivity, and detection of unoccupied states. In this work, we developed in situ synchrotron radiation soft X-ray absorption spectroscopy (in situ sXAS) to probe the variation of electronic structure for a reaction system during N2 photoreduction. Nickel single-atom and ceria nanoparticle comodified reduced graphene oxide (CeO2/Ni-G) was designed as a model catalyst. In situ sXAS directly reveals the dynamic interfacial charge transfer of photogenerated electrons under illumination and the consequent charge accumulation at the catalytic active sites for N2 activation. This work provides a powerful tool to monitor the electronic structure evolution of active sites under reaction conditions for photocatalysis and beyond.

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