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1.
Microbiol Spectr ; : e0062521, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34612668

RESUMO

Metabolomics is a powerful tool that can systematically describe global changes in the metabolome of microbes, thus improving our understanding of the mechanisms of action of antibiotics and facilitating the development of next-generation antibacterial therapies. However, current sample preparation methods are not efficient or reliable for studying the effects of antibiotics on microbes. In the present study, we reported a novel sample preparation approach using cold methanol/ethylene glycol for quenching Escherichia coli, thus overcoming the loss of intracellular metabolites caused by cell membrane damage. After evaluating the extraction efficiency of several extraction methods, we employed the optimized workflow to profile the metabolome of E. coli exposed to cephalexin. In doing so, we proved the utility of the proposed approach and provided insights into the comprehensive metabolic alterations associated with antibiotic treatment. IMPORTANCE The emergence and global spread of multidrug-resistant bacteria and genes are a global problem. It is critical to understand the interactions between antibiotics and bacteria and find alternative treatments for infections when we are moving closer to a postantibiotic era. It has been demonstrated that the bacterial metabolic environment plays an important role in the modulation of antibiotic susceptibility and efficacy. In the present study, we proposed a novel metabolomic approach for intracellular metabolite profiling of E. coli, which can be used to investigate the metabolite alterations of bacteria caused by antibiotic treatment. Further understanding of antibiotic-induced perturbations of bacterial metabolism would facilitate the discovery of new therapeutic targets and pathways.

2.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638623

RESUMO

How herbivorous insects adapt to host plants is a key question in ecological and evolutionary biology. The fall armyworm, (FAW) Spodoptera frugiperda (J.E. Smith), although polyphagous and a major pest on various crops, has been reported to have a rice and corn (maize) feeding strain in its native range in the Americas. The species is highly invasive and has recently established in China. We compared behavioral changes in larvae and adults of a corn population (Corn) when selected on rice (Rice) and the molecular basis of these adaptational changes in midgut and antennae based on a comparative transcriptome analysis. Larvae of S. frugiperda reared on rice plants continuously for 20 generations exhibited strong feeding preference for with higher larval performance and pupal weight on rice than on maize plants. Similarly, females from the rice selected population laid significantly more eggs on rice as compared to females from maize population. The most highly expressed DEGs were shown in the midgut of Rice vs. Corn. A total of 6430 DEGs were identified between the populations mostly in genes related to digestion and detoxification. These results suggest that potential adaptations for feeding on rice crops, may contribute to the current rapid spread of fall armyworm on rice crops in China and potentially elsewhere. Consistently, highly expressed DEGs were also shown in antennae; a total of 5125 differentially expressed genes (DEGs) s were identified related to the expansions of major chemosensory genes family in Rice compared to the Corn feeding population. These results not only provide valuable insight into the molecular mechanisms in host plants adaptation of S. frugiperda but may provide new gene targets for the management of this pest.

3.
Eur J Med Chem ; 226: 113859, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34601246

RESUMO

Urea transporters (UTs) have been identified as new targets for diuretics. Functional deletion of UTs led to urea-selective urinary concentrating defects with relative salt sparing. In our previous study, a UT inhibitor with a diarylamide scaffold, which is denoted as 11a, was demonstrated as the first orally available UT inhibitor. However, the oral bioavailability of 11a was only 4.38%, which obstructed its clinical application. In this work, by replacing the nitro group of 11a with an acetyl group, 25a was obtained. Compared with 11a, 25a showed a 10 times stronger inhibitory effect on UT-B (0.14 µM vs. 1.41 µM in rats, and 0.48 µM vs. 5.82 µM in mice) and a much higher inhibition rate on UT-A1. Moreover, the metabolic stability both in vitro and in vivo and the drug-like properties (permeability and solubility) of 25a were obviously improved compared with those of 11a. Moreover, the bioavailability of 25a was 15.18%, which was 3 times higher than that of 11a, thereby resulting in significant enhancement of the diuretic activities in rats and mice. 25a showed excellent potential for development as a promising clinical diuretic candidate for targeting UTs to treat diseases that require long-term usage of diuretics, such as hyponatremia.

4.
Front Public Health ; 9: 733458, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621722

RESUMO

Background: Employees who are physically present but work insufficiently because of illness are deemed as having presenteeism. In the health care setting, the issue has taken on greater importance because of the impairment of the physical and mental health of nurses and the nursing safety of the patients. According to the Job Demand-Resource Model, burnout may link emotional labor with presenteeism. Thus, this study analyzed the role of burnout as a mediating factor between the three types of emotional labor strategies and presenteeism among nurses in tertiary-level hospitals. Methods: A cross-sectional study of 1,038 nurses from six Chinese hospitals was conducted. The questionnaires, including the 14-item emotional labor strategies scale, 22-item Maslach Burnout Inventory scale, 6-item Stanford Presenteeism Scale, and items about demographic characteristics and work-related factors, were used to collect data. A multivariable linear regression was used to predict work-related factors and investigate the correlation of emotional labor, burnout, and presenteeism. The structural equation model was implemented to test the mediating effects of job burnout. Results: The results of the study showed that the average presenteeism score of the participants was 14.18 (4.33), which is higher than in Spanish, Portuguese, and Brazilian nurses. Presenteeism was explained by 22.8% of the variance in the final model in multivariable linear regression (P < 0.01). Presenteeism was found to be positively correlated with surface acting, emotionally expressed demands, deep acting, emotional exhaustion, depersonalization, and low personal accomplishment (P < 0.01). Notably, presenteeism was negatively correlated with deep acting (P < 0.01). In addition, burnout partially mediated the correlation between emotionally expressed demands, deep acting, and presenteeism with a mediatory effect of 24 and 63.31% of the total effect. Burnout completely mediated the association between surface acting and presenteeism, a mediating effect of 86.44% of the total effect. Conclusions: The results of this study suggested that different emotional labor strategies affect presenteeism, either directly or indirectly. Nursing managers should intervene to reduce presenteeism by improving the ability of the nurses to manage emotions, thereby alleviating burnout.

5.
Genes (Basel) ; 12(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34680888

RESUMO

Cyperus esculentus is widely representing one of the important oil crops around the world, which provides valuable resources of edible tubers called tiger nut. The chemical composition and high ability to produce fats emphasize the role of tiger nut in promoting oil crop productivity. However, the underlying molecular mechanism of the production and accumulation of lipids in tiger nut development still remains unclear. Here, we conducted comprehensive transcriptomics and lipidomics analyses at different developmental stages of tuber in Cyperus esculentus. Lipidomic analyses confirmed that the accumulation of lipids including glycolipids, phospholipids, and glycerides were significantly enriched during tuber development from early to mature stage. The proportion of phosphatidylcholines (PC) declined during all stages and phosphatidyl ethanolamine (PE) was significantly declined in early and middle stages. These findings implied that PC is actively involved in triacylglycerol (TAG) biosynthesis during the tubers development, whereas PE may participate in TAG metabolism during early and middle stages. Comparative transcriptomics analyses indicated several genomic and metabolic pathways associated with lipid metabolism during tuber development in tiger nut. The Pearson correlation analysis showed that TAG synthesis in different developmental stages was attributed to 37 candidate transcripts including CePAH1. The up-regulation of diacylglycerol (DAG) and oil content in yeast, resulted from the inducible expression of exogenous CePAH1 confirmed the central role of this candidate gene in lipid metabolism. Our results demonstrated the foundation of an integrative metabolic model for understanding the molecular mechanism of tuber development in tiger nut, in which lipid biosynthesis plays a central role.

6.
J Affect Disord ; 296: 622-634, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34688026

RESUMO

RATIONALE/IMPORTANCE: Researches have highlighted communication deficits between resting-state brain networks in major depressive disorder (MDD), as reflected in abnormal functional connectivity (FC). However, it is unclear whether impaired FC is associated with MDD pathology or is simply incidental to MDD symptoms. Moreover, there is no generalized theory to analyze the impact of treatment modalities on MDD. OBJECTIVES: To address the issues, we conducted a systematic review of 49 eligible papers to provide insight into the pathological mechanisms of MDD patients by summarizing resting-state FC alterations involving mood and cognitive abnormalities and the effects of medications on them. RESULTS: Mood disorders in MDD were characterized by abnormal FC between the amygdala, insula, anterior cingulate cortex (ACC), and prefrontal cortex (PFC). Cognitive impairment manifests as deficits in executive function, attention, memory, and rumination, primarily modulated by dysfunction between the fronto-parietal network and default mode network. Especially, we proposed the set of core abnormal FC (CA-FC) contributing to mood and cognitive impairment in MDD, currently including ACC-left precuneus/amygdala, rostral ACC-left dorsolateral PFC, left subgenual ACC-left cerebellar, left PFC- anterior subcallosal, and left precuneus-left pulvinar. After treatment, patients with normalized CA-FC showed remission of depressive symptoms. CONCLUSIONS: We propose a CA-FC set for possible causative principle of MDD, which unifies the FC results from specific, difficult-to-analyze conditions into one outcome set for screening. Furthermore, CA-FC varies from person to person, and the low success rate of a single treatment may be due to the inability to cover too many CA-FC.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34668690

RESUMO

Optical security involving the use of light to achieve distinctive vision effects has become a widely used approach for anticounterfeiting. Holographic multiplexing has attracted considerable interest in multiplexing security due to its high degree of freedom for manipulating the optical parameters of incident laser beams. However, the complex and time-consuming fabrication process of metasurface-based holograms and the sophisticated nature of holographic imaging systems have hindered the practical application of holographic multiplexing in anticounterfeiting. Combining holography with shape memory polymers to construct reconfigurable holograms provides a simple and efficient way for holographic multiplexing. This paper proposes a reconfigurable four-level amplitude hologram fabricated on a heat-shrinkable shape memory polymer using spatially modulated femtosecond laser pulses. Simply by triggering the shape recovery of the polymer through heating, the amplitude modulation of light by the hologram is reconfigured through the shrinking of processed microcrater pixels with three diameters, which enables variation to be achieved in reconstructed holographic images. Examples of holographic multiplexing and data encryption are used to validate the proposed method. The proposed economic and simple approach for holographic multiplexing provides an integrated and single-material solution to packaging and optical security, which has extensive potential in anticounterfeiting and optical encryption.

8.
Opt Lett ; 46(19): 4916-4919, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598233

RESUMO

Integral imaging, as an excellent light-field three-dimensional (3D) imaging technique, is considered as one of the most important technologies for 3D encryption because of its obvious advantages of high robustness, security, and computational feasibility. However, to date, there is no effective cryptanalysis technology for the light-field 3D cryptosystem. In this Letter, a cryptanalysis algorithm based on deep learning for the light-field 3D cryptosystem is presented. The 3D image can be optically retrieved by the trained network model without encryption keys. The experimental results verify the feasibility and effectiveness of our proposed method.

9.
Sci Total Environ ; : 151037, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34666086

RESUMO

Waste electrical and electronic equipment (WEEE) plastics not only pollute the environment, but are challenging to treat in an environmentally friendly manner. Biodegradation by insect larvae is potentially an eco-friendly method to treat WEEE plastics, but information about the feeding preference of insect larvae to WEEE plastics is lacking. In this study, a total of nine WEEE and pristine plastics were chosen to feed larvae of the following two insect species, i.e. Galleria mellonella and Tenebrio molitor. G. mellonella larvae significantly favor corresponding pristine plastics compared to two types of WEEE plastics, waste rigid polyurethane (RPU) and waste polystyrene (PS). One possible explanation is the increased chlorine or metals in the WEEE plastics measured using X-ray fluorescence spectrometer analysis. Scanning electron microscopy and Fourier transform infrared spectroscopy show that the destruction of physical structures and changes in surface functional groups were found in the two types of WEEE plastics in the larval frass, implying that the larvae partly biodegraded the plastics. Meanwhile, the powdered waste high impact polystyrene plastics (WHIPS) were ingested, but not the lumpy ones, indicating that the consumption by G. mellonella larvae is improved by the WHIPS physical modification. In addition, G. mellonella larvae presented the following decreasing preference for pristine plastics under individual-plastic-fed mode: RPU > phenol-formaldehyde resin > polyethylene (PE) > polypropylene > PS ≈ polyvinyl chloride; this is possibly due to differences in physical properties and chemical structures of the plastics; feeding preference of the larvae under multiple-plastics-fed mode is relatively consistent to that under individual-plastic-fed mode. Interestingly, the consumption by G. mellonella larvae of PE is higher than that of PS, while T. molitor larvae showed the opposite trend, implying that insect larvae have different plastics preference. The findings provide insights into biodegradation of WEEE plastics by insect larvae.

10.
Front Med (Lausanne) ; 8: 677029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660617

RESUMO

Introduction: Post-radical-hysterectomy (RH) patients suffer from a series of problems resulting from neurovascular injury, such as bladder dysfunction, which reduce their quality of life. We have designed this study to evaluate the efficacy of transcutaneous electrical stimulation (TENS) on patient rehabilitation after RH for early cervical cancer. Materials and methods: A total of 97 patients were enrolled in a randomized-controlled trial (from January 2015 to December 2019) involving 7 medical centers nationwide. Patients were assigned to either the intervention group (n = 46), or the control group (n = 51). TENS was given to patients in the intervention group from the 7th day after surgery for a total of 14-21 days. The control group received no TENS. Primary outcomes were measured for residual urine volume and recovery of urination function. Secondary outcomes were measures for urodynamics (UDS), pelvic floor electromyography function examination (PFEmF), and quality of life (QoL). Results: Residual urine volume and improvement in the rate of urination were found to show no significant differences on the 14th, 21st, and 28th days after surgery. The maximum flow rate (Qmax) in the intervention group was significantly higher than that in the control group on the 28th day, but there were no significant differences in average flow rate, voiding time, time to Qmax, muscle fiber strength, muscle fiber fatigue, and the abnormal rate of A3 reflection on the 28th day and the 3rd mo., as well as in the QoL at 3rd mo., 6th mo., and 12th mo. after surgery. Conclusion: Our study showed no sufficient evidence to prove that TENS under the trialed parameters could improve the subject's voiding function, PFEmF, and QOL after RH. This has provided valuable data for rehabilitation after RH. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02492542.

11.
Comput Intell Neurosci ; 2021: 9969322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475950

RESUMO

To explore the influence of weather conditions on the choice of the intercity travel mode of travelers, four modes of traveler transportation were studied in Xi'an, China, in March 2019: airplane, high-speed rail, conventional train, and express bus. The individual characteristics of travelers and intercity travel activity data were obtained, and they were matched with the weather characteristics at the departure time of the travelers. The Bayesian multinomial logit regression was employed to explore the relationship between the travel mode choice and weather characteristics. The results showed that temperature, relative humidity, rainfall, wind, air quality index, and visibility had significant effects on the travel mode selection of travelers, and the addition of these variables could improve the model's predictive performance. The research results can provide a scientific decision basis for traveler flow transfer and the prediction of traffic modes choice due to the effects of climate change.


Assuntos
Poluição do Ar , Poluição do Ar/análise , Teorema de Bayes , Transportes , Viagem , Tempo (Meteorologia)
12.
ACS Omega ; 6(34): 22103-22113, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34497902

RESUMO

Studies have shown that anaerobic digestion (AD) has an effect on the liquid and solid product property of sequential pyrolysis, but its influence on the gaseous products is lacking. In this study, syngas produced by pyrolysis from three raw organic solid wastes and the corresponding digestates, i.e., food waste, vinasse, and cow manure were investigated. AD causes a decrease in the contents of volatile solid, fixed carbon, C, H, and N and an increase in the S content. The weight loss of the wastes mainly occurs at 200-550 °C during the pyrolysis and the loss of the food waste and vinasse is higher than that of cow manure. In the carbon (C)-containing gas, AD leads to a decrease in the CH4 content of the syngas, implying that the heat values of the digestates are lower than that of the raw substrates. After AD, the total amount of nitrogen (N)-containing gas from the vinasse increases by 40.1%, while that from cow manure decreases by 14.1%. On the contrary, the total amount of sulfur (S)-containing groups in the syngas from vinasse drop by 22.0%, while that from cow manure increases by 9.1%. In addition, slight changes in the C-, N-, and S-containing gases are found from food waste. The results indicate that AD has a different effect on the N- and S- containing gaseous groups from different organic solid wastes, and the mechanisms deserve further investigation. The findings supply a theoretical foundation for environmental-friendly application of syngas from the digestates.

13.
ACS Appl Mater Interfaces ; 13(38): 45224-45235, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34519480

RESUMO

Peripheral arterial disease (PAD) is a progressive atherosclerotic disorder characterized by blockages of the arteries supplying the lower extremities. Ischemia initiates oxidative damage and mitochondrial dysfunction in the legs of PAD patients, causing injury to the tissues of the leg, significant decline in walking performance, leg pain while walking, and in the most severe cases, nonhealing ulcers and gangrene. Current clinical trials based on cells/stem cells, the trophic factor, or gene therapy systems have shown some promising results for the treatment of PAD. Biomaterial matrices have been explored in animal models of PAD to enhance these therapies. However, current biomaterial approaches have not fully met the essential requirements for minimally invasive intramuscular delivery to the leg. Ideally, a biomaterial should present properties to ameliorate oxidative stress/damage and failure of angiogenesis. Recently, we have created a thermosensitive hyaluronic acid (HA) hydrogel with antioxidant capacity and skeletal muscle-matching stiffness. Here, we further optimized HA hydrogels with the cell adhesion peptide RGD to facilitate the development of vascular-like structures in vitro. The optimized HA hydrogel reduced intracellular reactive oxygen species levels and preserved vascular-like structures against H2O2-induced damage in vitro. HA hydrogels also provided prolonged release of the vascular endothelial growth factor (VEGF). After injection into rat ischemic hindlimb muscles, this VEGF-releasing hydrogel reduced lipid oxidation, regulated oxidative-related genes, enhanced local blood flow in the muscle, and improved running capacity of the treated rats. Our HA hydrogel system holds great potential for the treatment of the ischemic legs of patients with PAD.

14.
Nat Commun ; 12(1): 5350, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504089

RESUMO

Relationships between biodiversity and multiple ecosystem functions (that is, ecosystem multifunctionality) are context-dependent. Both plant and soil microbial diversity have been reported to regulate ecosystem multifunctionality, but how their relative importance varies along environmental gradients remains poorly understood. Here, we relate plant and microbial diversity to soil multifunctionality across 130 dryland sites along a 4,000 km aridity gradient in northern China. Our results show a strong positive association between plant species richness and soil multifunctionality in less arid regions, whereas microbial diversity, in particular of fungi, is positively associated with multifunctionality in more arid regions. This shift in the relationships between plant or microbial diversity and soil multifunctionality occur at an aridity level of ∼0.8, the boundary between semiarid and arid climates, which is predicted to advance geographically ∼28% by the end of the current century. Our study highlights that biodiversity loss of plants and soil microorganisms may have especially strong consequences under low and high aridity conditions, respectively, which calls for climate-specific biodiversity conservation strategies to mitigate the effects of aridification.


Assuntos
Biodiversidade , Clima Desértico , Fungos/metabolismo , Desenvolvimento Vegetal , Plantas/metabolismo , Solo/química , China , Ecossistema , Fungos/classificação , Fungos/crescimento & desenvolvimento , Geografia , Concentração de Íons de Hidrogênio , Modelos Teóricos , Plantas/classificação , Microbiologia do Solo , Especificidade da Espécie , Água/metabolismo
15.
Small ; 17(41): e2102102, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34510724

RESUMO

Neuroinflammation is critically involved in the repair of spinal cord injury (SCI), and macrophages associated with inflammation propel the degeneration or recovery in the pathological process. Currently, efforts have been focused on obtaining efficient therapeutic anti-inflammatory drugs to treat SCI. However, these drugs are still unable to penetrate the blood spinal cord barrier and lack the ability to target lesion areas, resulting in unsatisfactory clinical efficacy. Herein, a polymer-based nanodrug delivery system is constructed to enhance the targeting ability. Because of increased expression of matrix metalloproteinases (MMPs) in injured site after SCI, MMP-responsive molecule, activated cell-penetrating peptides (ACPP), is introduced into the biocompatible polymer PLGA-PEI-mPEG (PPP) to endow the nanoparticles with the ability for diseased tissue-targeting. Meanwhile, etanercept (ET), a clinical anti-inflammation treatment medicine, is loaded on the polymer to regulate the polarization of macrophages, and promote locomotor recovery. The results show that PPP-ACPP nanoparticles possess satisfactory lesion targeting effects. Through inhibited consequential production of proinflammation cytokines and promoted anti-inflammation cytokines, ET@PPP-ACPP could decrease the percentage of M1 macrophages and increase M2 macrophages. As expected, ET@PPP-ACPP accumulates in lesion area and achieves effective treatment of SCI; this confirmed the potential of nano-drug loading systems in SCI immunotherapy.

16.
J Plant Physiol ; 266: 153529, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34583134

RESUMO

Potassium is a major cationic nutrient involved in numerous physiological processes in plants. The uptake of K+ is mediated by K+ channels and transporters, and the Shaker K+ channel gene family plays an essential role in K+ uptake and stress resistance in plants. However, little is known regarding this family in soybean. In this study, 14 members of the Shaker K+ channel gene family were identified in soybean and were classified into five groups. Protein domain analysis revealed that Shaker K+ channel gene members have an ion transport domain (ion trans), a cyclic nucleotide-binding domain, ankyrin repeat domains, and a dimerization domain in the potassium ion channel. Quantitative real-time polymerase chain reaction analysis indicated that the expression of eight genes (notably GmAKT1) in soybean leaves and roots was significantly increased in response to salt and drought stress. Furthermore, the overexpression of GmAKT1 in Arabidopsis enhanced root length, K+ concentration, and fresh/dry weight ratio compared with wild-type plants subjected to salt and drought stress; this suggests that GmAKT1 improves the tolerance of soybean to abiotic stress. Our results provide important insight into the characterization of Shaker K+ channel gene family members in soybean and highlight the function of GmAKT1 in soybean plants under salt and drought stress.

17.
Photochem Photobiol Sci ; 20(10): 1323-1331, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34562235

RESUMO

To meet the requirements of theranostics with diagnosis and treatment, photodynamic-based therapy is simultaneously enabled with the incorporation of methylene blue (MB) as imaging agent and photosensitizer in core-shell structured drug vehicles. Citrate-modified hydroxyapatite (HAp) powders are first grafted with ß-cyclodextrin (CD), then combined with MB molecules through electrostatic interactions, and finally encapsulated with carbon shells through hydro-thermal carbonization of glucose to prepare HAp-CD-MB@C powders. Processing parameters of carbonization temperature, glucose addition, reaction time and CD addition are varied to prepare drug carriers with modulated crystallite degrees and photo-physical properties. Increased crystallite sizes of HAp are accompanied with the formation of C=O, C=C and C-OH groups in carbon shell, endowing sustainable release behaviors of MB through carbonous structures. High photoluminescence intensities are fairly related with red-shifted vibration peaks of groups in tightly combined MB molecules through hydrogen bonds. This hydrogen bonding effect is significantly increased for HAp-CD-MB@C140 with the splitting of CH3-involved vibration peaks in infrared spectra, which causes increase in photoluminescence intensity and four-fold increase in generation ratio of singlet oxygen. The present studies shed light on preparation of core-shell structured drug carriers, modulation of aggregate states of MB molecules, enhancement of photo-physical properties and improvement of generation ratio of singlet oxygen during photodynamic-based therapy.


Assuntos
Carbono/química , Hidroxiapatitas/química , Azul de Metileno/química , beta-Ciclodextrinas/química , Cristalização , Portadores de Fármacos/química , Glucose/química , Ligação de Hidrogênio , Azul de Metileno/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/metabolismo , Oxigênio Singlete/química , Temperatura
18.
J Am Soc Nephrol ; 32(9): 2159-2174, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34465607

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by numerous cysts originating from renal tubules and is associated with significant tubular epithelial cell proliferation. Focal adhesion kinase (FAK) promotes tumor growth by regulating multiple proliferative pathways. METHODS: We established the forskolin (FSK)-induced three-dimensional (3D) Madin-Darby Canine Kidney cystogenesis model and 8-bromoadenosine-3`,5`-cyclic monophosphate-stimulated cyst formation in ex vivo embryonic kidney culture. Cultured human renal cyst-lining cells (OX-161) and normal tubular epithelial cells were treated with FAK inhibitors or transfected with green fluorescent protein-tagged FAK mutant plasmids for proliferation study. Furthermore, we examined the role of FAK in two transgenic ADPKD animal models, the kidney-specific Pkd1 knockout and the collecting duct-specific Pkd1 knockout mouse models. RESULTS: FAK activity was significantly elevated in OX-161 cells and in two ADPKD mouse models. Inhibiting FAK activity reduced cell proliferation in OX-161 cells and prevented cyst growth in ex vivo and 3D cyst models. In tissue-specific Pkd1 knockout mouse models, FAK inhibitors retarded cyst development and mitigated renal function decline. Mechanically, FSK stimulated FAK activation in tubular epithelial cells, which was blocked by a protein kinase A (PKA) inhibitor. Inhibition of FAK activation by inhibitors or transfected cells with mutant FAK constructs interrupted FSK-mediated Src activation and upregulation of ERK and mTOR pathways. CONCLUSIONS: Our study demonstrates the critical involvement of FAK in renal cyst development, suggests that FAK is a potential therapeutic target in treating patients with ADPKD, and highlights the role of FAK in cAMP-PKA-regulated proliferation.

19.
Biomaterials ; 276: 121070, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34418817

RESUMO

Sentinel lymph node (SLN) imaging and biopsy has been advocated as an important technique to evaluate the metastatic status of regional lymph nodes and determine subsequent surgical procedure for many cancers, yet there is no reliable means to provide accurate and rapid diagnosis of metastatic SLN during surgery. Here we develop a new approach, named "Ratiometric Raman dual-nanotag strategy", that using folic acid functionalized targeted and nontargeted gap-enhanced Raman tags (FA-GERTs and Nt-GERTs) to detect metastatic SLN based on Raman imaging combined with classical least square data processing methods. By using this strategy, with built-in self-calibration for signal correction, rather than absolute intensity-dependent signal readout, we realize the visualization and prompt intraoperative diagnosis of metastatic SLN with a high accuracy of 87.5 % when the cut-off value of ratio (FA-GERTs/Nt-GERTs) set at 1.255. This approach may outperform the existing histopathological assessment in diagnosing SLN metastasis and is promising for guiding surgical procedure in the future.


Assuntos
Linfonodo Sentinela , Diagnóstico por Imagem , Humanos , Linfonodos , Metástase Linfática , Biópsia de Linfonodo Sentinela
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