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Miniaturized reconstructive spectrometers play a pivotal role in on-chip and portable devices, offering high-resolution spectral measurement through precalibrated spectral responses and AI-driven reconstruction. However, two key challenges persist for practical applications: artificial intervention in algorithm parameters and compatibility with complementary metal-oxide-semiconductor (CMOS) manufacturing. We present a cutting-edge miniaturized reconstructive spectrometer that incorporates a self-adaptive algorithm referenced with Fabry-Perot resonators, delivering precise spectral tests across the visible range. The spectrometers are fabricated with CMOS technology at the wafer scale, achieving a resolution of ~2.5 nm, an average wavelength deviation of ~0.27 nm, and a resolution-to-bandwidth ratio of ~0.46%. Our approach provides a path toward versatile and robust reconstructive miniaturized spectrometers and facilitates their commercialization.
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Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.
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BACKGROUND: Vascular calcification (VC) is suggested to be associated with serum klotho levels in patients with maintenance hemodialysis (MHD), whereas there is a lack of reports on the associations of VC status in whole arteries with serum klotho contents. METHODS: One hundred forty eligible patients with MHD and a total of age-and gender-matched normal controls (NCs) were recruited. We analyzed the VC statuses of large arteries and peripheral muscular arteries by calculating the sum of scores from each artery. The levels of serum klotho were determined by ELISA. In addition, the relationship between serum klotho and VC status was evaluated using correlation analysis and regression analysis. RESULTS: The VC severity in MHD patients tended to be worse in comparison with NCs. Serum klotho level in patients with MHD was lower than that in the NC subjects (âP < 0.0001), which was correlated with VC scores as reflected by correlation analysis and regression analysis. Serum klotho concentrations exhibited a dynamic decline along with increased VC status stages. Subjects with higher levels of serum klotho had a higher prevalence of cardiovascular events. CONCLUSION: Our study indicates serum klotho is strongly associated with VC status in a stage-dependent manner.
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Glucuronidase , Calcificação Vascular , Humanos , Proteínas Klotho , Diálise Renal , ArtériasRESUMO
Herein, a photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of 2-(acetoacetoxy)ethyl methacrylate (AEMA) in ethanol/water at room temperature for in situ preparation of ß-ketoester-functionalized block copolymer nano-objects is reported. AEMA is also copolymerized with isobornyl methacrylate (IBOMA) to improve the colloidal stability of PIBOMA-based block copolymer nano-objects prepared by photoinitiated RAFT dispersion polymerization at low temperatures. A series of P(IBOMA-stat-AEMA)-based block copolymer nano-objects are prepared by changing reaction parameters. Finally, lanthanide-doped block copolymer nano-objects with luminescent and magnetic properties are also prepared based on the complexation of various lanthanide ions with the ß-ketoester group. It is expected that the current study will provide a facile platform for the in situ preparation of ß-ketoester-functionalized block copolymer nano-objects with different morphologies for specific applications.
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Metacrilatos , Polímeros , Polimerização , ÁguaRESUMO
Heat shock transcription factor 1 (HSF1) deficiency aggravates cardiac remodeling under pressure overload. However, the mechanism is still unknown. Here we employed microRNA array analysis of the heart tissue of HSF1-knockout (KO) mice to investigate the potential roles of microRNAs in pressure overload-induced cardiac remodeling under HSF-1 deficiency, and the profiles of 478 microRNAs expressed in the heart tissues of adult HSF1-KO mice were determined. We found that the expression of 5 microRNAs was over 2-fold higher expressed in heart tissues of HSF1-KO mice than in those of wild-type (WT) control mice. Of the overexpressed microRNAs, miR-195a-3p had the highest expression level in HSF1-null endothelial cells (ECs). Induction with miR-195a-3p in ECs significantly suppressed CD31 and VEGF, promoted AngII-induced EC apoptosis, and impaired capillary-like tube formation. In vivo, the upregulation of miR-195a-3p accentuated cardiac hypertrophy, increased the expression of ß-MHC and ANP, and compromised systolic function in mice under pressure overload induced by transverse aortic constriction (TAC). By contrast, antagonism of miR-195a-3p had the opposite effect on HSF1-KO mice. Further experiments confirmed that AMPKα2 was the direct target of miR-195a-3p. AMPKα2 overexpression rescued the reduction of eNOS and VEGF, and the impairment of angiogenesis that was induced by miR-195a-3p. In addition, upregulation of AMPKα2 in the myocardium of HSF1-null mice by adenovirus-mediated gene delivery enhanced CD31, eNOS and VEGF, reduced ß-MHC and ANP, alleviated pressure overload-mediated cardiac hypertrophy and restored cardiac function. Our findings revealed that the upregulation of miR-195a-3p due to HSF1 deficiency impaired cardiac angiogenesis by regulating AMPKα2/VEGF signaling, which disrupted the coordination between the myocardial blood supply and the adaptive hypertrophic response and accelerated the transition from cardiac hypertrophy to heart failure in response to pressure overload.
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Cardiomegalia/patologia , Células Endoteliais/metabolismo , Insuficiência Cardíaca/patologia , Fatores de Transcrição de Choque Térmico/deficiência , MicroRNAs/metabolismo , Miocárdio/patologia , Neovascularização Fisiológica , Pressão , Regiões 3' não Traduzidas/genética , Adenilato Quinase/metabolismo , Animais , Apoptose , Sequência de Bases , Cardiomegalia/complicações , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/metabolismo , Fatores de Transcrição de Choque Térmico/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Modelos Biológicos , Miócitos Cardíacos/metabolismo , Regulação para Cima , Remodelação VentricularRESUMO
Mechanical overload can be classified into pressure overload and volume overload, causing concentric and eccentric cardiac hypertrophy, respectively. Here, we aimed to differentiate the load-mediated signaling pathways involved in pressure versus volume overload cardiac hypertrophy. Pressure or volume overload was imposed on C57BL/6J mice by transverse aortic constriction (TAC) or aortic regurgitation (AR), respectively. After surgery (2 wk), left ventricular structure and function were evaluated by echocardiographic, hemodynamic, and histological analyses. Signaling pathways related to hypertrophy, fibrosis, angiogenesis, and apoptosis were studied by histological analysis, RT-PCR, and Western blot analysis. Although mean wall stress was similar in both TAC and AR mice, systolic wall stress was significantly increased in TAC and diastolic wall stress was mainly elevated in AR. TAC or AR induced concentric or eccentric compensated hypertrophy, respectively. TAC was associated with more significant fibrosis and apoptosis, whereas AR was associated with more significant angiogenesis. MAPK kinase family, ß-arrestin-2, Akt, and Ca2+-related signaling pathways were markedly activated in TAC but mildly upregulated or unchanged in AR. Pressure overload and volume overload induce different phenotypic and molecular adaptations in cardiac hypertrophy. Most load-related signaling pathways assessed in this study predominate in pressure but not volume overload. The stimulus-specific heterogeneity in the signaling pathways requires distinct manipulations for further mechanistic and pharmacological studies. NEW & NOTEWORTHY Using the transverse aortic constriction mouse model and the newly developed aortic regurgitation mouse model, we delineated the prominent differences between concentric and eccentric cardiac hypertrophy on morphological, functional, and molecular levels. Our findings are important for the precise diagnosis and treatment of these two types of cardiac hypertrophy. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/chinese-english-language-podcast-on-differential-cardiac-remodeling-in-tac-vs-ar/ .
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Aorta/fisiopatologia , Insuficiência da Valva Aórtica/complicações , Pressão Arterial , Hipertrofia Ventricular Esquerda/etiologia , Contração Miocárdica , Miocárdio/metabolismo , Transdução de Sinais , Função Ventricular Esquerda , Remodelação Ventricular , Adaptação Fisiológica , Animais , Aorta/cirurgia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/metabolismo , Insuficiência da Valva Aórtica/fisiopatologia , Fenômenos Biomecânicos , Constrição , Modelos Animais de Doenças , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Fenótipo , Estresse MecânicoRESUMO
Colistin therapy is used as the last line of defense against life-threatening Gram-negative infections. Nephrotoxicity is the major dose-limiting side effect that impedes optimal dosing of patients. This study aims to examine the nephroprotective effect of the plasma volume expander gelofusine against colistin-induced nephrotoxicity. Renal protection was assessed in mice that were subcutaneously injected with colistin sulfate (14 mg/kg of body weight × 6 doses every 2 h; accumulated dose, 84 mg/kg) and simultaneously injected in the intraperitoneal region with gelofusine (75, 150, 300, or 600 mg/kg × 6). At 2 and 20 h after the last colistin dose, mice were euthanized, and the severity of renal alteration was examined histologically. Histological findings in mice revealed that colistin-induced nephrotoxicity was ameliorated by gelofusine in a dose-dependent manner, whereas significant histological abnormalities were detected in the kidneys of mice in the colistin-only group. The impact of coadministered gelofusine on colistin pharmacokinetics was investigated in rats. Rats were administered a single intravenous dose of gelofusine at 400 mg/kg 15 min prior to the intravenous administration of colistin (1 mg/kg). Gelofusine codosing did not alter the pharmacokinetics of colistin in rats; however, gelofusine did significantly lower the accumulation of colistin in the kidney tissue of mice. This is the first study demonstrating the protective effect of gelofusine against colistin-induced nephrotoxicity. These findings highlight the clinical potential of gelofusine as a safe adjunct for ameliorating the nephrotoxicity and increasing the therapeutic index of polymyxins.
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Antibacterianos/toxicidade , Colistina/farmacocinética , Colistina/toxicidade , Necrose do Córtex Renal/induzido quimicamente , Necrose do Córtex Renal/prevenção & controle , Substitutos do Plasma/uso terapêutico , Poligelina/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Colistina/farmacologia , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Rim/efeitos dos fármacos , Rim/lesões , Necrose do Córtex Renal/tratamento farmacológico , Masculino , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
In mice, myocardial hypertrophic preconditioning (HP), which is produced by the removal of short-term transverse aortic constriction (TAC), was recently reported to render the heart resistant to hypertrophic responses induced by subsequent reconstriction (Re-TAC). However, there is no efficient noninvasive method for ensuring that the repeated aortic manipulations were successfully performed. We previously demonstrated that ultrasound biomicroscopy (UBM) is a noninvasive and effective approach for predicting TAC success. Here, we investigated the value of UBM for serial predictions of load conditions in establishing a murine HP model. C57BL/6J mice were subjected to a sham operation, TAC, or Re-TAC, and the peak flow velocity at the aortic banding site (PVb) was measured by UBM. Left ventricular end-systolic pressure (LVESP) was examined by micromanometric catheterization. The PVb was positively associated with LVESP (R2 = 0.8204, P < 0.001, for TAC at 3 days and R2 = 0.7746, P < 0.001, for Re-TAC at 4 wk). PVb and LVESP values were markedly elevated after aortic banding, became attenuated to the sham-operated level after debanding, and increased after aortic rebanding. The cardiac hypertrophic responses were examined by UBM, histology, RT-PCR, and Western blot analysis. Four weeks after the last operation, with PVb ≥ 3.5 m/s as an indicator of successful aortic constriction, Re-TAC mice showed less cardiac hypertrophy, fetal gene expression, and ERK1/2 activation than TAC mice. Therefore, we successfully established a UBM protocol for the serial assessment of aortic flow and the prediction of LVESP during repeated aortic manipulations in mice, which might be useful for noninvasive evaluations of the murine HP model.NEW & NOTEWORTHY We successfully developed an ultrasound biomicroscopy protocol for the serial assessment of aortic bandings and the relevant left ventricular pressure in a murine model of cardiac hypertrophic preconditioning. The protocol may be of great importance in the successful establishment of the hypertrophic preconditioning model for further mechanistic and pharmacological studies.
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Aorta/fisiopatologia , Cardiomiopatia Hipertrófica/fisiopatologia , Modelos Animais de Doenças , Precondicionamento Isquêmico Miocárdico/métodos , Microscopia Acústica , Animais , Aorta/diagnóstico por imagem , Aorta/patologia , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/prevenção & controle , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Volume Sistólico , Resultado do TratamentoRESUMO
To improve the solubility and bioavailability of oridonin (ORI), glycerol monooleate lipid (GMO)- or phytantriol (PYT)-Poloxamer 407-propylene glycol-water systems were firstly used to develop cubosomes containing ORI for oral delivery. These cubosomes prepared through the fragmentation of bulk gels under homogenization conditions of 1200 bar and nine cycles had a mean particle size of around 200 nm with narrow size distribution, and ORI encapsulation efficiency over 85%. Powder X-ray diffraction and differential scanning calorimetry indicated that ORI was in an amorphous or molecular form in the cubosomes. The internal structures of GMO- and PYT-based cubosomes were revealed by small-angle X-ray scattering as a bi-continuous cubic liquid crystalline phase with Im3m and Pn3m geometry, respectively. About 80% of ORI was released in vitro from GMO- and PYT-based cubosomes at 24 h, showing a sustained release kinetics fitted with Higuchi's equation. The pharmacokinetic study in rats showed that the PYT-based cubosomes significantly enhanced the adsorption of ORI as compared to the GMO-based cubosomes and ORI suspension, with evidence of longer half-life and greater relative bioavailability (p < 0.01). Therefore, the PYT-based cubosomes containing ORI might be proposed as a promising candidate carrier for the efficient delivery of drug with therapeutic treatment.
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Diterpenos do Tipo Caurano/administração & dosagem , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Álcoois Graxos/química , Glicerídeos/química , Administração Oral , Animais , Diterpenos do Tipo Caurano/sangue , Diterpenos do Tipo Caurano/química , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Estrutura Molecular , Tamanho da Partícula , Ratos Endogâmicos , Propriedades de SuperfícieRESUMO
Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and its primary treatment strategy is to lower IOP by medication. Current ocular drug delivery in treating glaucoma is confronting a variety of challenges, such as low corneal permeability and bioavailability due to the unique anatomical structure of the human eye. To tackle these challenges, a cubosome drug delivery system for glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM cubosomes (liquid crystalline nanoparticles) were prepared using glycerol monooleate and poloxamer 407 via high-pressure homogenization. These constructed nanoparticles appeared spherical using transmission electron microscopy and had an average particle size of 142 nm, zeta potential of -6.27 mV, and over 85% encapsulation efficiency. Moreover, using polarized light microscopy and small-angle X-ray scattering (SAXS), it was shown that the TM cubosomes have cubic liquid crystalline D-type (Pn3m) structure, which provides good physicochemical stability and high encapsulation efficiency. Ex vivo corneal permeability experiments showed that the total amount of TM cubosomes penetrated was higher than the commercially available eye drops. In addition, in vivo studies revealed that TM cubosomes reduced the IOP in rabbits from 27.8â¼39.7 to 21.4â¼32.6 mmHg after 1-week administration and had a longer retention time and better lower-IOP effect than the commercial TM eye drops. Furthermore, neither cytotoxicity nor histological impairment in the rabbit corneas was observed. This study suggests that cubosomes are capable of increasing the corneal permeability and bioavailability of TM and have great potential for ocular disease treatment.
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Córnea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Timolol/administração & dosagem , Timolol/síntese química , Administração Oftálmica , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/síntese química , Animais , Córnea/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Humanos , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/síntese química , Soluções Oftálmicas/toxicidade , Tamanho da Partícula , Coelhos , Espalhamento a Baixo Ângulo , Timolol/toxicidade , Difração de Raios XRESUMO
BACKGROUND: Docetaxel resistance remains a major obstacle in the treatment of non-small cell lung cancer (NSCLC). High-mobility group box 1 (HMGB1) has been shown to promote autophagy protection in response to antitumor therapy, but the exact molecular mechanism underlying HMGB1-mediated autophagy has not been clearly defined. METHODS: Lung adenocarcinoma (LAD) cells were transfected with pcDNA3.1-HMGB1 or HMGB1 shRNA, followed by docetaxel treatment. Cell viability and proliferation were tested by MTT assay and colony formation assay, respectively. Annexin V flow cytometric analysis and western blot analysis of activated caspase3 and cleaved PARP were used to evaluate apoptosis, while immunofluorescence microscopy and transmission electron microscopy were applied to assess autophagy activity. The formation of the Beclin-1-PI3K-III complex was examined by immunoprecipitation analysis. NOD/SCID mice were inoculated with docetaxel-resistant SPC-A1/DTX cells transfected with control or HMGB1 shRNA. RESULTS: HMGB1 translocated from the nucleus to the cytoplasm in LAD cells exposed to docetaxel and acted as a positive regulator of autophagy, which inhibited apoptosis and increased drug resistance. Suppression of HMGB1 restored the sensitivity of LAD cells to docetaxel both in vivo and in vitro. Mechanistic investigation revealed that HMGB1 promoted the formation of the Beclin-1-PI3K-III complex through activating the mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating autophagosome formation. CONCLUSIONS: Our results demonstrated that HMGB1-regulated autophagy is a significant contributor to docetaxel resistance in LAD cells. Suppression of HMGB1 or limiting HMGB1 cytosolic translocation diminished autophagic protection in response to docetaxel in LAD cells.
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Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Autofagia/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína HMGB1/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Taxoides/farmacologia , Adenocarcinoma/enzimologia , Adenocarcinoma/ultraestrutura , Adenocarcinoma de Pulmão , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Linhagem Celular Tumoral , Citoproteção/efeitos dos fármacos , Citosol/efeitos dos fármacos , Citosol/metabolismo , Docetaxel , Regulação para Baixo/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/ultraestrutura , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos NOD , Camundongos SCID , Modelos Biológicos , Complexos Multiproteicos/metabolismo , Fosfatidilinositol 3-Quinases , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
It was previously thought that ncRNA could not encode polypeptides, but recent reports have challenged this notion. As research into ncRNA progresses, it is increasingly clear that it serves roles beyond traditional mechanisms, playing significant regulatory roles in various diseases, notably cancer, which is responsible for 70% of human deaths. Numerous studies have highlighted the diverse regulatory mechanisms of ncRNA that are pivotal in cancer initiation and progression. The role of ncRNA-encoded polypeptides in cancer regulation has gained prominence. This article explores the newly identified regulatory functions of these polypeptides in three types of ncRNA-lncRNA, pri-miRNA, and circRNA. These polypeptides can interact with proteins, influence signaling pathways, enhance miRNA stability, and regulate cancer progression, malignancy, resistance, and other clinical challenges. Furthermore, we discuss the evolutionary significance of these polypeptides in the transition from RNA to protein, examining their emergence and conservation throughout evolution.
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Neoplasias , Peptídeos , RNA não Traduzido , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Circular/genética , RNA Circular/metabolismo , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de SinaisRESUMO
Introduction: The escalating prevalence of bacterial resistance, particularly multidrug-resistant bacteria like Acinetobacter baumannii, has become a significant global public health concern. The CRISPR-Cas system, a crucial defense mechanism in bacteria against foreign genetic elements, provides a competitive advantage. Type I-Fb and Type I-Fa are two subtypes of CRISPR-Cas systems that were found in A. baumannii, and the I-Fb CRISPR-Cas system regulates antibiotic resistance in A. baumannii. However, it is noteworthy that a majority of clinical isolates of A. baumannii lack or have incomplete CRISPR-Cas systems and most of them are multidrug-resistant. In light of this, our study aimed to examine the impact of antibiotic pressure on the fitness cost of the I-Fb CRISPR-Cas system in A. baumannii. Methods and Results: In the study, we conducted in vitro competition experiments to investigate the influence of sub-minimum inhibitory concentration (sub-MIC) on the CRISPR-Cas systems' fitness cost in A. baumannii. We found that the fitness cost of the CRISPR-Cas system was increased under sub-MIC conditions. The expression of CRISPR-Cas-related genes was decreased, while the conjugation frequency was increased in AB43 under sub-MIC conditions. Through metabolomic analysis, we identified that sub-MIC conditions primarily affected energy metabolism pathways. In particular, we observed increased carbon metabolism, nitrogen metabolism, and intracellular ATP. Notably, the CRISPR-Cas system demonstrated resistance to the efflux pump-mediated resistance. Furthermore, the expression of efflux pump-related genes was increased under sub-MIC conditions. Conclusion: Our findings suggest that the I-Fb CRISPR-Cas system confers a significant competitive advantage in A. baumanni. However, under sub-MIC conditions, its function and the ability to inhibit the energy required for efflux pumps are reduced, resulting in an increased fitness cost and loss of competitive advantage.
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Metal organic framework (MOF) films have attracted abundant attention due to their unique characters compared with MOF particles. But the high-temperature reaction and solvent corrosion limit the preparation of MOF films on fragile substrates, hindering further applications. Fabricating macro-sized continuous free-standing MOF films and transferring them onto fragile substrates are a promising alternative but still challenging. Here, a universal strategy to prepare transferrable macro-sized continuous free-standing MOF films with the assistance of oxide nanomembranes prepared by atomic layer deposition and studied the growth mechanism is developed. The oxide nanomembranes serve not only as reactant, but also as interfacial layer to maintain the integrality of the free-standing structure as the stacked MOF particles are supported by the oxide nanomembrane. The centimeter-scale free-standing MOF films can be transferred onto fragile substrates, and all in one device for glucose sensing is assembled. Due to the strong adsorption toward glucose molecules, the obtained devices exhibit outstanding performance in terms of high sensitivity, low limit of detection, and long durability. This work opens a new window toward the preparation of MOF films and MOF film-based biosensor chip for advantageous applications in post-Moore law period.
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Técnicas Biossensoriais , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Glucose , Desenho de Equipamento/métodosRESUMO
Alzheimer's disease (AD) is characterized by a gradual decline in cognitive function and memory impairment, significantly impacting the daily lives of patients. Rivastigmine (RHT), a cholinesterase inhibitor, is used to treat mild to moderate AD via oral administration. However, oral administration is associated with slow absorption rate and severe systemic side effects. RHT nasal spray (RHT-ns), as a nose-to-brain delivery system, is more promising for AD management due to its efficient brain delivery and reduced peripheral exposure. This study constructed RHT-ns for enhancing AD treatment efficacy, and meanwhile the correlation between drug olfactory deposition and drug entering into the brain was explored. A 3D-printed nasal cast was employed to quantify the drug olfactory deposition. Brain delivery of RHT-ns was quantified using fluorescence tracking and Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) analysis, which showed a good correlation to the olfactory deposition. F2 (containing 1% (w/v) viscosity modifier Avicel® RC-591) with high olfactory deposition and drug brain delivery was further investigated for pharmacodynamics study. F2 exhibited superiority in AD treatment over the commercially available oral formulation. In summary, the present study showed the successful development of RHT-ns with improved olfactory deposition and enhanced brain delivery. It might provide new insight into the design and development of nose-to-brain systems for the treatment of AD.
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Doença de Alzheimer , Humanos , Rivastigmina/química , Rivastigmina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Sprays Nasais , Administração Intranasal , Encéfalo , Inibidores da ColinesteraseRESUMO
Lactic acid (LA) is an important downstream product of glycolysis in living cells and is abundant in our body fluids, which are strongly associated with diseases. The development of enzyme-free LA sensors with high sensitivity and low consumption remains a challenge. 2D metal-organic frameworks (MOFs) are considered to be promising electrochemical sensing materials and have attracted much attention in recent years. Compared to monometallic MOFs, the construction of bimetallic MOFs (BMOFs) can obtain a larger specific surface area, thereby increasing the exposed active site. 3D petal-like NixCoy MOF films on nickel foams (NixCoy BMOF@Ni foams) are successfully prepared by combining atomic layer deposition-assisted technology and hydrothermal strategy. The established NixCoy BMOF@Ni foams demonstrate noticeable LA sensing activity, and the study is carried out on behalf of the Ni1Co5 BMOF@Ni foam, which has a sensitivity of up to 9030 µA mM-1 cm-2 with a linear range of 0.01-2.2 mM and the detection limit is as low as 0.16 µM. Additionally, the composite has excellent stability and repeatability for the detection of LA under a natural air environment with high accuracy and reliability. Density functional theory calculation is applied to study the reaction process between composites and LA, and the result suggests that the active site in the NiCo BMOF film favors the adsorption of LA relative to the active site of monometallic MOF film, resulting in improved performance. The developed composite has a great potential for the application of noninvasive LA biosensors.
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Introduction: Chronic kidney disease (CKD) is worldwide healthcare burden with growing incidence and death rate. Emerging evidence demonstrated the compositional and functional differences of gut microbiota in patients with CKD. As such, gut microbial features can be developed as diagnostic biomarkers and potential therapeutic target for CKD. Methods: To eliminate the outcome bias arising from factors such as geographical distribution, sequencing platform, and data analysis techniques, we conducted a comprehensive analysis of the microbial differences between patients with CKD and healthy individuals based on multiple samples worldwide. A total of 980 samples from six references across three nations were incorporated from the PubMed, Web of Science, and GMrepo databases. The obtained 16S rRNA microbiome data were subjected to DADA2 processing, QIIME2 and PICRUSt2 analyses. Results: The gut microbiota of patients with CKD differs significantly from that of healthy controls (HC), with a substantial decrease in the microbial diversity among the CKD group. Moreover, a significantly reduced abundance of bacteria Faecalibacterium prausnitzii (F. prausnitzii) was detected in the CKD group through linear discriminant analysis effect size (LEfSe) analysis, which may be associated with the alleviating effects against CKD. Notably, we identified CKD-depleted F. prausnitzii demonstrated a significant negative correlation with three pathways based on predictive functional analysis, suggesting its potential role in regulating systemic acidbase disturbance and pro-oxidant metabolism. Discussion: Our findings demonstrated notable alterations of gut microbiota in CKD patients. Specific gut-beneficial microbiota, especially F. prausnitzii, may be developed as a preventive and therapeutic tool for CKD clinical management.
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Microbioma Gastrointestinal , RNA Ribossômico 16S , Insuficiência Renal Crônica , Microbioma Gastrointestinal/genética , Humanos , RNA Ribossômico 16S/genética , Insuficiência Renal Crônica/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Fezes/microbiologia , Filogenia , Faecalibacterium prausnitzii/genética , Biodiversidade , Disbiose/microbiologiaRESUMO
The limitations of solvent residues, unmanageable film growth regions, and substandard performance impede the extensive utilization of metal-organic framework (MOF) films for biosensing devices. Here, we report a strategy for ion design in gas-phase synthesized flexible MOF porous film to attain universal regulation of biosensing performances. The key fabrication process involves atomic layer deposition of induced layer coupled with lithography-assisted patterning and area-selective gas-phase synthesis of MOF film within a chemical vapor deposition system. Sensing platforms are subsequently formed to achieve specific detection of H2O2, dopamine, and glucose molecules by respectively implanting Co, Fe, and Ni ions into the network structure of MOF films. Furthermore, we showcase a practical device constructed from Co ions-implanted ZIF-4 film to accomplish real-time surveillance of H2O2 concentration at mouse wound. This study specifically elucidates the electronic structure and coordination mode of ion design in MOF film, and the obtained knowledge aids in tuning the electrochemical property of MOF film for advantageous sensing devices.
Assuntos
Técnicas Biossensoriais , Dopamina , Técnicas Eletroquímicas , Peróxido de Hidrogênio , Estruturas Metalorgânicas , Técnicas Biossensoriais/métodos , Estruturas Metalorgânicas/química , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Técnicas Eletroquímicas/métodos , Animais , Camundongos , Dopamina/análise , Dopamina/química , Glucose/análise , Glucose/isolamento & purificação , Glucose/química , Cobalto/química , Níquel/química , Íons/químicaRESUMO
Photodetection has attracted significant attention for information transmission. While the implementation relies primarily on the photonic detectors, they are predominantly constrained by the intrinsic bandgap of active materials. On the other hand, photothermoelectric (PTE) detectors have garnered substantial research interest for their promising capabilities in broadband detection, owing to the self-driven photovoltages induced by the temperature differences. To get higher performances, it is crucial to localize light and heat energies for efficient conversion. However, there is limited research on the energy conversion in PTE detectors at micro/nano scale. In this study, we have achieved a two-order-of-magnitude enhancement in photovoltage responsivity in the self-rolled tubular tellurium (Te) photodetector with PTE effect. Under illumination, the tubular device demonstrates a maximum photovoltage responsivity of 252.13 V W-1 and a large detectivity of 1.48 × 1011 Jones. We disclose the mechanism of the PTE conversion in the tubular structure with the assistance of theoretical simulation. In addition, the device exhibits excellent performances in wide-angle and polarization-dependent detection. This work presents an approach to remarkably improve the performance of photodetector by concentrating light and corresponding heat generated, and the proposed self-rolled devices thus hold remarkable promises for next-generation on-chip photodetection.
RESUMO
Ever-evolving advancements in films have fueled many of the developments in the field of electrochemical sensors. For biosensor application platforms, the fabrication of metal-organic framework (MOF) films on microscopically structured substrates is of tremendous importance. However, fabrication of MOF film-based electrodes always exhibits unsatisfactory performance, and the mechanisms of the fabrication and sensing application of the corresponding composites also need to be explored. Here, we report the fabrication of conformal MIL-53 (Fe) films on carbonized natural seaweed with the assistance of an oxide nanomembrane and a potential-dependent electrochemical dopamine (DA) sensor. The geometry and structure of the composite can be conveniently tuned by the experimental parameters, while the sensing performance is significantly influenced by the applied potential. The obtained sensor demonstrates ultrahigh sensitivity, a wide linear range, a low limit of detection, and a good distinction between DA and ascorbic acid at an optimized potential of 0.3 V. The underneath mechanism is investigated in detail with the help of theoretical calculations. This work bridges the natural material and MOF films and is promising for future biosensing applications.