RESUMEN
The excited-state property determines the occurrence of photofunctions in organic materials. We have developed a fragment frontier molecular orbital model for the donor-acceptor-type (D-A-type) systems and constructed molecular descriptors of the excited-state property with charge transfer (CT) or local excitation (LE) based on the orbital information on constituent D and A fragments. Applying these descriptors, we rapidly screened 1CT or 1LE and 3CT or 3LE molecules from 2500 molecules generated by the binding of 50 donors and 50 acceptors, and the results of 26 molecules were confirmed by available experiments and first-principles calculations. Moreover, the modulation of these descriptors by chemical groups allows the rational design of target excited states. This work is significant for high-throughput screening of excellent organic photofunctional materials from a giant chemical database.
RESUMEN
BACKGROUND: The quality of low-light endoscopic images involves applications in medical disciplines such as physiology and anatomy for the identification and judgement of tissue structures. Due to the use of point light sources and the constraints of narrow physiological structures, medical endoscopic images display uneven brightness, low contrast, and a lack of texture information, presenting diagnostic challenges for physicians. METHODS: In this paper, a nonlinear brightness enhancement and denoising network based on Retinex theory is designed to improve the brightness and details of low-light endoscopic images. The nonlinear luminance enhancement module uses higher-order curvilinear functions to improve overall brightness; the dual-attention denoising module captures detailed features of anatomical structures; and the color loss function mitigates color distortion. RESULTS: Experimental results on the Endo4IE dataset demonstrate that the proposed method outperforms existing state-of-the-art methods in terms of Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Learned Perceptual Image Patch Similarity (LPIPS). The PSNR is 27.2202, SSIM is 0.8342, and the LPIPS is 0.1492. It provides a method to enhance image quality in clinical diagnosis and treatment. CONCLUSIONS: It offers an efficient method to enhance images captured by endoscopes and offers valuable insights into intricate human physiological structures, which can effectively assist clinical diagnosis and treatment.
Asunto(s)
Relación Señal-Ruido , Humanos , Endoscopía/métodos , Aumento de la Imagen/métodos , Algoritmos , Dinámicas no Lineales , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical-genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl-2-keto-b-D-erythro-pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment.
RESUMEN
The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research.
Asunto(s)
Bibliometría , Membrana Corioalantoides , Neoplasias , Animales , Embrión de Pollo , Neoplasias/veterinaria , Humanos , Investigación Biomédica , Modelos Animales de EnfermedadRESUMEN
Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional profiling to systematically analyze natural killer (NK) cell surface receptors, we identify leukocyte immunoglobulin like receptor B1 (LILRB1) as a critical checkpoint receptor that defines a TB-associated cell subset (LILRB1+ NK cells) and drives NK cell exhaustion in TB. Mechanistically, Mtb-infected macrophages display high expression of human leukocyte antigen-G (HLA-G), which upregulates and activates LILRB1 on NK cells to impair their functions by inhibiting mitogen-activated protein kinase (MAPK) signaling via tyrosine phosphatases SHP1/2. Furthermore, LILRB1 blockade restores NK cell-dependent anti-Mtb immunity in immuno-humanized mice. Thus, LILRB1-HLA-G axis constitutes a NK cell immune checkpoint in TB and serves as a promising immunotherapy target.
Asunto(s)
Antígenos HLA-G , Células Asesinas Naturales , Receptor Leucocitario Tipo Inmunoglobulina B1 , Mycobacterium tuberculosis , Tuberculosis , Receptor Leucocitario Tipo Inmunoglobulina B1/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Antígenos HLA-G/metabolismo , Antígenos HLA-G/genética , Antígenos HLA-G/inmunología , Humanos , Animales , Tuberculosis/inmunología , Tuberculosis/microbiología , Ratones , Mycobacterium tuberculosis/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Antígenos CDRESUMEN
In this study, three types of dodecyl chitosan quaternary ammonium salts, each with different spacer groups were synthesized. These chitosan derivatives are N',N'-dimethyl-N'-dodecyl-ammonium chloride-N-amino-acetyl chitosan (DMDAC), N'-dodecyl-N-isonicotinyl chitosan chloride (DINCC) and N',N'-dimethyl-N'-dodecyl-ammonium chloride-N-benzoyl chitosan (DMDBC). The synthesized products were characterized using Fourier transform infrared spectrometers, nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis. The antibacterial and antibiofilm activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated. The experimental results indicated that the introduction of hydrophobic groups of spacer groups could enhance the antibacterial and antibiofilm activities of the chitosan derivatives. The antibacterial rates of the chitosan derivatives were over 90 % for both E. coli and S. aureus at a concentration of 0.5 mg/mL. The chitosan derivatives removed >50 % of the mature biofilm of E. coli and over 90 % of the mature biofilm of S. aureus at a concentration of 2.5 mg/mL. Further, the synthesized chitosan derivatives were determined to be non-toxic to L929 cells. Among them, DMDBC exhibited the most promising overall performance and show potential for wide-ranging applications in food preservation, disinfectants, medical, and other fields.
Asunto(s)
Antibacterianos , Biopelículas , Quitosano , Escherichia coli , Pruebas de Sensibilidad Microbiana , Compuestos de Amonio Cuaternario , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Quitosano/análogos & derivados , Biopelículas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Compuestos de Amonio Cuaternario/síntesis química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Espectroscopía Infrarroja por Transformada de Fourier , RatonesRESUMEN
Chitosan exhibits good biocompatibility and some antibacterial activity, making it a popular choice in biomedicine, personal care products, and food packaging. Despite its advantages, the limited antibacterial effectiveness of chitosan hinders its widespread use. Introducing a six-membered heterocyclic structure through chemical modification can significantly enhance its antimicrobial properties and broaden its potential applications. In order to explore the effect of six-membered heterocyclic structure on the antibacterial and antibiofilm activities of chitosan. In this study, seven chitosan derivatives containing six-membered heterocyclics were prepared. They were characterized using Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis. Cell viability assay showed that they were non-toxic. The antibacterial and antibiofilm activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were evaluated. Our research findings demonstrate that increasing the hydrophobicity, alkalinity and charge density of the substitute groups improved the antibacterial and antibiofilm activities of chitosan. This study also offers valuable insights into the quantitative structure-activity relationships of chitosan derivatives in terms of antibacterial and antibiofilm activities.
Asunto(s)
Antibacterianos , Biopelículas , Quitosano , Escherichia coli , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Escherichia coli/efectos de los fármacos , Biopelículas/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Supervivencia Celular/efectos de los fármacos , Humanos , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase1,2. However, BDQ also inhibits human ATP synthase3. At present, how these compounds interact with either M. tuberculosis ATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosis ATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosis ATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase and M. tuberculosis ATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs.
Asunto(s)
Antituberculosos , Diarilquinolinas , Imidazoles , ATPasas de Translocación de Protón Mitocondriales , Mycobacterium tuberculosis , Piperidinas , Piridinas , Humanos , Antituberculosos/farmacología , Antituberculosos/química , Sitios de Unión , Microscopía por Crioelectrón , Diarilquinolinas/química , Diarilquinolinas/farmacología , Imidazoles/química , Imidazoles/farmacología , ATPasas de Translocación de Protón Mitocondriales/antagonistas & inhibidores , ATPasas de Translocación de Protón Mitocondriales/química , ATPasas de Translocación de Protón Mitocondriales/metabolismo , ATPasas de Translocación de Protón Mitocondriales/ultraestructura , Modelos Moleculares , Mycobacterium tuberculosis/enzimología , Mycobacterium tuberculosis/efectos de los fármacos , Piperidinas/química , Piperidinas/farmacología , Subunidades de Proteína/metabolismo , Subunidades de Proteína/química , Subunidades de Proteína/antagonistas & inhibidores , Piridinas/química , Piridinas/farmacologíaRESUMEN
Drought-induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked. We quantified the vulnerability to drought-induced embolism, pressure-volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads. Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads. Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits - particularly vessels - may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads.
Asunto(s)
Cycadopsida , Sequías , Hojas de la Planta , Agua , Xilema , Xilema/fisiología , Xilema/anatomía & histología , Hojas de la Planta/anatomía & histología , Hojas de la Planta/fisiología , Cycadopsida/fisiología , Cycadopsida/anatomía & histología , Especificidad de la EspecieRESUMEN
In the process of human aging, significant age-related changes occur in brain tissue. To assist individuals in assessing the degree of brain aging, screening for disease risks, and further diagnosing age-related diseases, it is crucial to develop an accurate method for predicting brain age. This paper proposes a multi-scale feature fusion method called Tri-UNet based on the U-Net network structure, as well as a brain region information fusion method based on multi-channel input networks. These methods address the issue of insufficient image feature learning in brain neuroimaging data. They can effectively utilize features at different scales of MRI and fully leverage feature information from different regions of the brain. In the end, experiments were conducted on the Cam-CAN dataset, resulting in a minimum Mean Absolute Error (MAE) of 7.46. The results demonstrate that this method provides a new approach to feature learning at different scales in brain age prediction tasks, contributing to the advancement of the field and holding significance for practical applications in the context of elderly education.
Asunto(s)
Envejecimiento , Encéfalo , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Envejecimiento/fisiología , Anciano , Persona de Mediana Edad , Adulto , Masculino , Femenino , Neuroimagen/métodos , Anciano de 80 o más Años , Procesamiento de Imagen Asistido por Computador/métodos , Adulto Joven , AlgoritmosRESUMEN
BACKGROUND: A long-term follow-up of close contacts to monitor their infection status is essential to formulate a promising screening strategy. The study aimed to assess the dynamics of tuberculosis (TB) infection using Interferon-γ release assay (IGRA) and determine risk factors associated with TB infection. METHODS: Definite TB patients were interviewed and their household contacts were screened for TB infection by IGRA during 12-month longitudinal investigation. RESULTS: We included in our analyses 184 household contacts of 92 index TB patients. 87 individuals (47.3%) in contact group progressed to TB infection, of whom 86 developed into IGRA positive within 24 weeks. Close contacts with a higher age and comorbidities are easier to exhibit TB infection. Analysis showed that risk factors for becoming IGRA-positive individuals included residence, older age, comorbidities, BCG scar and high bacterial load. Contacts with BCG scar had a lower IGRA-positive rate. CONCLUSION: IGRA conversion generally occurs within 24 weeks after exposure. The TB transmission happens since subclinical TB stage and the presence of BCG scar is an independent protective factor reducing risk of TB infection among close contacts. Repeated IGRA tests are sensible to conducted among close contacts at 24 weeks after exposure to identify the IGRA-positive individuals.
Asunto(s)
Trazado de Contacto , Ensayos de Liberación de Interferón gamma , Tuberculosis , Humanos , Masculino , Femenino , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Factores de Riesgo , Tuberculosis/epidemiología , Tuberculosis/transmisión , Adulto Joven , Anciano , Adolescente , Mycobacterium tuberculosis , Estudios Longitudinales , Composición FamiliarRESUMEN
The most frequent adverse event associated with bedaquiline (BDQ) is the QTc interval prolongation; however, there was no biomarkers that could be used to predict the occurrence of QTc prolongation in BDQ-treated patients. In this study, we employed the ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) to generate metabolic profiling for the discovery of potential predictive urine biomarkers of QTc prolongation in these patients. Untargeted metabolomic technique was used to concentrate the differential metabolic pathway, and targeted metabolomic technique was subsequently performed to identify predictive biomarkers for QTc prolongation. A total of 45 rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB) patients were enrolled in our study, including 15 RR/MDR-TB patients with QTc interval prolongation (QIP) and 30 RR/MDR-TB patients with QTc interval un-prolongations (QIU). Untargeted technique revealed that the lipid metabolism was the most differential metabolic pathway between two groups. Further targeted technique identified four differential metabolites, including betaine, LPE (18:2), LPE (20:3), and LPE (20:4). The combined analysis of metabolisms revealed that the combined use of LPE (20:3) and LPE (20:4) had the best performance for predicting the occurrence of QTc prolongation in TB patients, yielding a sensitivity of 87.4% and a specificity of 78.5%. In addition, with the progression of BDQ treatment, the LPEs exhibited persistent difference in the BDQ-treated TB patients experiencing QTc interval prolongation. In conclusion, our data demonstrate that the combined use of LPE (20:3) and LPE (20:4) yields promising performance for predicting the occurrence of QTc interval prolongation in BDQ-treated patients.
RESUMEN
Chitosan quaternary phosphine salts (NPCS) were synthesized with enhanced antimicrobial properties using a two-step method. Composite films (CNSP) were prepared by incorporating NPCS and polyvinyl alcohol (PVA) as the base material, citric acid as the crosslinker and functional additive, exhibiting antibacterial and UV-blocking properties. The composite film showed a maximum tensile strength of 20.4 MPa, an elongation at break of 677%, and a UV light barrier transmittance of 70%. Application of these composite membranes in preserving strawberries demonstrated effectiveness in maintaining freshness by preventing water loss, inhibiting microbial growth, and extending shelf life. In addition, the composite film demonstrated biosafety. These results indicate that CNSP composite films holds significant promise for safe and sustainable food packaging applications.
Asunto(s)
Quitosano , Ácido Cítrico , Embalaje de Alimentos , Conservación de Alimentos , Fragaria , Alcohol Polivinílico , Alcohol Polivinílico/química , Fragaria/química , Quitosano/química , Quitosano/farmacología , Ácido Cítrico/química , Ácido Cítrico/farmacología , Embalaje de Alimentos/instrumentación , Conservación de Alimentos/métodos , Conservación de Alimentos/instrumentación , Antibacterianos/farmacología , Antibacterianos/química , Reactivos de Enlaces Cruzados/química , Resistencia a la TracciónRESUMEN
N-(sodium 2-hydroxypropylsulfonate) chitosan (HSCS), N-sulfonate chitosan (SCS) and N-isonicotinic sulfonate chitosan (ISCS) were prepared. The structures of the prepared chitosan derivatives were characterized by nuclear magnetic resonance (1H NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and elemental analysis (EA). Antibacterial and antibiofilm activities of these chitosan derivatives were evaluated in vitro. The minimum inhibitory concentration (MIC) of HSCS and SCS against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were 0.625 mg/mL and 0.156 mg/mL, respectively. ISCS exhibited MIC values of 0.313 mg/mL and 0.078 mg/mL against E. coli and S. aureus, respectively. ISCS demonstrated superior antibacterial and antibiofilm properties compared to SCS and HSCS. These findings suggest that the incorporation of a pyridine structure into sulfonate chitosan enhances its antibacterial and antibiofilm activities, and the prepared ISCS has a promising application prospect for controlling the reproduction of microorganisms in the field of food packaging.
Asunto(s)
Antibacterianos , Biopelículas , Quitosano , Escherichia coli , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Quitosano/síntesis química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Biopelículas/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Ácidos Sulfónicos/química , Ácidos Sulfónicos/farmacología , Ácidos Sulfónicos/antagonistas & inhibidoresRESUMEN
Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.
RESUMEN
AIM: To assess the performance of macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and 10-2 visual field (VF) parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma. METHODS: Totally 127 eyes from 89 participants (36 eyes of 19 healthy participants, 45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients) were included. The relationships between the optical coherence tomography (OCT)-derived parameters and VF sensitivity were determined. Patients with early glaucoma were divided into eyes with or without central 10° of the VF damages (CVFDs), and the diagnostic performances of OCT-derived parameters were assessed. RESULTS: In early glaucoma, the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation (PSD; with average mGCIPLT: ß=-0.046, 95%CI, -0.067 to -0.024, P<0.001). In advanced glaucoma, the mGCIPLT was related to the 24-2 VF mean deviation (MD; with average mGCIPLT: ß=0.397, 95%CI, 0.199 to 0.595, P<0.001), 10-2 VF MD (with average mGCIPLT: ß=0.762, 95%CI, 0.485 to 1.038, P<0.001) and 24-2 VF PSD (with average mGCIPLT: ß=0.244, 95%CI, 0.124 to 0.364, P<0.001). Except for the minimum and superotemporal mGCIPLT, the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs. The area under the curve (AUC) of the average mGCIPLT (AUC=0.949, 95%CI, 0.868 to 0.982) was greater than that of the average circumpapillary retinal nerve fiber layer thickness (cpRNFLT; AUC=0.827, 95%CI, 0.674 to 0.918) and rim area (AUC=0.799, 95%CI, 0.610 to 0.907) in early glaucomatous eyes with CVFDs versus normal eyes. CONCLUSION: The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF, cpRNFLT and ONH parameters, especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.
RESUMEN
Adherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn's disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.
Asunto(s)
Adhesión Bacteriana , Biopelículas , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli , Regulación Bacteriana de la Expresión Génica , Macrófagos , Macrófagos/microbiología , Animales , Ratones , Escherichia coli/genética , Escherichia coli/patogenicidad , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Biopelículas/crecimiento & desarrollo , Infecciones por Escherichia coli/microbiología , Humanos , Concentración de Iones de Hidrógeno , Virulencia , Colitis/microbiología , Enfermedad de Crohn/microbiología , Modelos Animales de Enfermedad , Transducción de Señal , Ácidos/metabolismoRESUMEN
The study aimed to create a low loading, high retention, easier to apply O/W mometasone furoate (MF) cream using a chemical enhancer (CE) approach to provide more options for patients with atopic dermatitis (AD) and to investigate molecular mechanisms of its increased release and retention. A Box-Behnken design determined the optimal formulation based on stability and in vitro skin retention. Evaluations included appearance, rheological properties, irritation, in vivo tissue distribution and pharmacodynamics. Molecular mechanisms of enhanced release were studied using high-speed centrifugation, molecular dynamics and rheology. The interaction between the CE, MF and skin was studied by tape stripping, CLSM, ATR-FTIR and SAXS. The formulation was optimized to contain 0.05% MF and used 10% polyglyceryl-3 oleate (POCC) as the CE. There was no significant difference from Elocon® cream in in vivo retention and pharmacodynamics but increased in vivo retention by 3.14-fold and in vitro release by 1.77-fold compared to the basic formulation. POCC reduced oil phase cohesive energy density, enhancing drug mobility and release. It disrupted skin lipid phases, aiding drug entry and formed hydrogen bonds, prolonging retention. This study highlights POCC as a CE in the cream, offering insights for semi-solid formulation development.
Asunto(s)
Liberación de Fármacos , Furoato de Mometasona , Crema para la Piel , Piel , Furoato de Mometasona/administración & dosificación , Furoato de Mometasona/farmacocinética , Furoato de Mometasona/química , Animales , Crema para la Piel/administración & dosificación , Crema para la Piel/química , Piel/metabolismo , Piel/efectos de los fármacos , Administración Cutánea , Masculino , Absorción Cutánea/efectos de los fármacos , Química Farmacéutica/métodos , Glicerol/química , Glicerol/análogos & derivados , Dermatitis Atópica/tratamiento farmacológico , Femenino , Excipientes/química , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/farmacocinética , Composición de Medicamentos/métodos , Ácido Oléico/química , Polímeros/químicaRESUMEN
Background: SARS-CoV-2, the cause of the COVID-19 pandemic, poses a significant threat to humanity. Individuals with pulmonary tuberculosis (PTB) are at increased risk of developing severe COVID-19, due to long-term lung damage that heightens their susceptibility to full-blown disease. Methods: Three COVID-19 datasets (GSE157103, GSE166253, and GSE171110) and one PTB dataset (GSE83456) were obtained from the Gene Expression Omnibus databases. Subsequently, data were subjected to weighted gene co-expression network analysis(WGCNA)followed by functional enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. These analyses revealed two overlapping disease-specific modules, each comprising co-regulated genes with potentially related biological functions. Using Cytoscape, we visualised the interaction network containing common disease-related genes found within the intersection between modules and predicted transcription factors (TFs). Real-time qPCR was conducted to quantify expression levels of these genes in blood samples from COVID-19 and PTB patients. Finally, DisGeNET and the Drug Signatures database were employed to analyze these common genes, unveiling their connections to clinical disease features and potential drug treatments. Results: Examination of the overlap between COVID-19 and PTB gene modules unveiled 11 common genes. Functional enrichment analyses using KEGG and GO shed light on potential functional relationships among these genes, providing insights into their potential roles in the heightened mortality of PTB patients due to SARS-CoV-2 infection. Furthermore, results of various bioinformatics-based analyses of common TFs and target genes led to identification of shared pathways and therapeutic targets for PTB patients with COVID-19, along with potential drug treatments for these patients. Conclusion: Our results unveiled a potential biological connection between COVID-19 and PTB, as supported by results of functional enrichment analysis that highlighted potential biological processes and signaling pathways shared by both diseases. Building on these findings, we propose potential drug treatments for PTB patients with COVID-19, pending verification of drug safety and efficacy through laboratory and multicentre studies before clinical use.