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BACKGROUND: Cervical cancer remains the second most common cause of death in women and poses a growing public health challenge. It is urgent to increase cervical cancer screening rates in Kenya as per the 2018 Kenya National Cancer Screening Guidelines. Addressing access to care may serve as a target to achieve this goal; however, how individual dimensions of access to care are associated with the utilization of cervical cancer screening services in low- and middle-income countries, including Kenya, remains unclear. This study aimed to examine how different aspects of access to care (affordability, availability, geographical access, and social influence) were associated with cervical cancer screening among Kenyan women of reproductive age. METHODS: This cross-sectional study used data from the 2014 Kenya Demographic and Health Survey and the 2010 Kenya Service Provision Assessment. The final sample included 5,563 women aged 25-49 years. Logistic regression models were used to examine the association between different aspects of access to care and the uptake of cervical cancer screening. RESULTS: Factors such as being in the poorest wealth quintile, lacking health insurance, having difficulty obtaining funds for treatment (affordability), limited availability of screening services at nearby facilities (availability), living in rural areas (geographical access), and having healthcare decisions made solely by husbands/partners or others (social influence) were associated with a decreased likelihood of the uptake of cervical cancer screening. CONCLUSIONS: Increasing health insurance coverage, enhancing the availability of screening services at health facilities, expanding mobile screening health facilities in rural areas, and empowering women to make their own healthcare decisions are crucial steps for increasing cervical cancer screening uptake in Kenya.
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Detección Precoz del Cáncer , Accesibilidad a los Servicios de Salud , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Kenia , Estudios Transversales , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Adulto , Detección Precoz del Cáncer/estadística & datos numéricos , Persona de Mediana Edad , Factores Socioeconómicos , Encuestas EpidemiológicasRESUMEN
AIMS: Examining the connection between the triglyceride-glucose (TyG) index and chronic kidney disease (CKD) was the aim of this investigation. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) covering the years 1999-2020 were analyzed in this study. The TyG index was calculated as Ln (triglycerides (mg/dl) * fasting glucose (mg/dl)/2). The two criteria used to diagnose CKD were low estimated glomerular filtration rate (eGFR) (eGFR < 60 mL/min/1.73m2) or albuminuria (urine albumin-to-creatinine ratio (ACR) ≥ 30 mg/g). To look into the independent associations between TyG index levels with CKD, albuminuria, and low-eGFR, weighted multivariable logistic regression and generalized additive models were employed. To assess and contrast the diagnostic ability, receiver operating characteristic (ROC) curves were employed. RESULTS: Out of 18,078 total participants recruited, 48.54% were male. 8.48 + 0.68 was the mean value of the TyG index. CKD, albuminuria, and low-eGFR were common, with respective prevalences of 17.06%, 11.26%, and 8.03%, respectively. The TyG index and CKD were observed to positively correlate (OR = 4.03; 95% CI 1.81, 8.96). In US adults between the ages of 41 and 60, a J-shaped connection was found between the two. Furthermore, a higher TyG index is associated with a higher prevalence of albuminuria (OR = 6.11; 95% CI 2.64, 14.14). Subgroup analyses and interaction tests revealed that different stratifications did not significantly affect the relationship between TyG index and CKD, albuminuria, and low-eGFR. Comparing the TyG index to other indicators [lipid accumulation product (LAP), Visceral adiposity index (VAI), and the triglyceride glucose-body mass index (TyG-BMI)], it may be more accurate and discriminative in predicting CKD and albuminuria. CONCLUSION: When predicting CKD and albuminuria, the TyG index may be a more useful marker when compared to other markers (LAP, VAI, and TyG-BMI index). In addition, in American adults aged 41-60, the TyG index shows a J-shaped relationship with CKD. As a result, when assessing the kidney health of US adults, we must pay close attention to the significance of the TyG index.
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Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before.
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Corteza Entorrinal , Neuronas , Navegación Espacial , Corteza Visual , Animales , Corteza Entorrinal/fisiología , Corteza Visual/fisiología , Navegación Espacial/fisiología , Ratones , Neuronas/fisiología , Masculino , Ratones Endogámicos C57BL , Estimulación Luminosa , Región CA1 Hipocampal/fisiología , Región CA1 Hipocampal/citología , Vías Visuales/fisiología , Percepción Visual/fisiologíaRESUMEN
Acinetobacter baumannii has developed multiple drug resistances, posing a significant threat to antibiotic efficacy. LysECD7, an endolysin derived from phages, could be a promising therapeutic agent against multi-drug resistance A. baumannii. In this study, in order to further enhance the antibacterial efficiency of the engineered LysECD7, a few lipopolysaccharide-interacting peptides (Li5, MSI594 and Li5-MSI) were genetically fused with LysECD7. Based on in vitro antibacterial activity, the fusion protein Lys-Li5-MSI was selected for further modifications aimed at extending its half-life. A cysteine residue was introduced into Lys-Li5-MSI through mutation (Lys-Li5-MSIV12C), followed by conjugation with a C16 fatty acid chain via a protonation substitution reaction(V12C-C16). The pharmacokinetic profile of V12C-C16 exhibited a more favorable characteristic in comparison to Lys-Li5-MSI, thereby resulting in enhanced therapeutic efficacy against lethal A. baumannii infection in mice. The study provides valuable insights for the development of novel endolysin therapeutics and proposes an alternative therapeutic strategy for combating A. baumannii infections.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Endopeptidasas , Lipopolisacáridos , Proteínas Recombinantes de Fusión , Animales , Femenino , Ratones , Acinetobacter baumannii/efectos de los fármacos , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Antibacterianos/farmacología , Antibacterianos/química , Modelos Animales de Enfermedad , Endopeptidasas/farmacología , Endopeptidasas/metabolismo , Endopeptidasas/química , Endopeptidasas/genética , Ácidos Grasos/metabolismo , Ácidos Grasos/química , Ácidos Grasos/farmacología , Lipopolisacáridos/metabolismo , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Péptidos/farmacología , Péptidos/química , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/químicaRESUMEN
Introduction: Monocyte-to-lymphocyte ratio (MLR) is a convenient and noninvasive inflammatory biomarker, and inflammation has been reported to be associated with prostate cancer (PCa). Our objective was to ascertain any possible correlation between PCa and MLR. Methods: We utilized data from the 1999-2020 cycles of the National Health and Nutrition Examination Survey (NHANES) regarding MLR and PCa. The independent associations of MLR and other inflammatory biomarkers (platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI)) with PCa was investigated using weighted multivariate logistic regression and generalized additive models. Receiver operating characteristic (ROC) curves were conducted to evaluate and contrast their diagnostic capabilities. Results: The analysis we conducted comprised 25,367 persons in total. The mean MLR was 0.31 ± 0.14. The prevalence of PCa was 3.1%. A positive association was found between MLR and PCa (OR = 2.28; 95% CI: 1.44, 3.62). According to the interaction tests, age, body mass index (BMI), hypertension, diabetes, and smoking status did not significantly impact the relationship between MLR and PCa (all p for interaction >0.05). ROC analysis showed that MLR had a stronger discriminative ability and accuracy in predicting PCa than other inflammatory biomarkers (NLR, SII, AISI, PLR, and SIRI). Conclusion: MLR might be better than other inflammatory biomarkers (NLR, SIRI, AISI, PLR, and SII) in predicting PCa. American adults who have elevated levels of MLR, NLR, PLR, SII, and AISI should be aware that they have a greater risk of PCa.
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Disorder of complement response is a significant pathogenic factor causing some autoimmune and inflammation diseases. The Ornithodoros moubata Complement Inhibitor (OmCI), a small 17 kDa natural protein, was initially extracted from soft tick salivary glands. The protein was found binding to complement C5 specifically, inhibiting the activation of the complement pathway, which is a successful therapeutic basis of complement-mediated diseases. However, a short half-life due to rapid renal clearance is a common limitation of small proteins for clinical application. In this study, we extended the half-life of OmCI by modifying it with fatty acid, which was a method used to improve the pharmacokinetics of native peptides and proteins. Five OmCI mutants were initially designed, and single-site cysteine mutation was introduced to each of them. After purification, four OmCI mutants were obtained that showed similar in vitro biological activities. Three mutants of them were subsequently coupled with different fatty acids by nucleophilic substitution. In total, 15 modified derivatives were screened and tested for anticomplement activity in vitro. The results showed that coupling with fatty acid would not significantly affect their complement-inhibitory activity (CH50 and AH50). OmCIT90C-CM02 and OmCIT90C-CM05 were validated as the applicable OmCI bioconjugates for further pharmacokinetic assessments, and both showed improved plasma half-life in mice compared with unmodified OmCI (15.86, 17.96 vs 2.57 h). In summary, our data demonstrated that OmCI conjugated with fatty acid could be developed as the potential long-acting C5 complement inhibitor in the clinic.
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Complemento C5 , Ácidos Grasos , Ornithodoros , Animales , Ácidos Grasos/química , Ratones , Complemento C5/antagonistas & inhibidores , Diseño de Fármacos , Semivida , Proteínas Inactivadoras de Complemento/farmacología , Proteínas Inactivadoras de Complemento/química , Inactivadores del Complemento/farmacología , Inactivadores del Complemento/farmacocinética , Inactivadores del Complemento/química , HumanosRESUMEN
Introduction: Our objective was to explore the potential link between systemic inflammation response index (SIRI) and chronic kidney disease (CKD). Methods: The data used in this study came from the National Health and Nutrition Examination Survey (NHANES), which gathers data between 1999 and 2020. CKD was diagnosed based on the low estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 or albuminuria (urinary albumin-to-creatinine ratio (ACR) of more than 30 mg/g). Using generalized additive models and weighted multivariable logistic regression, the independent relationships between SIRI and other inflammatory biomarkers (systemic immune-inflammation index (SII), monocyte/high-density lipoprotein ratio (MHR), neutrophil/high-density lipoprotein ratio (NHR), platelet/high-density lipoprotein ratio (PHR), and lymphocyte/high-density lipoprotein ratio (LHR)) with CKD, albuminuria, and low-eGFR were examined. Results: Among the recruited 41,089 participants, males accounted for 49.77% of the total. Low-eGFR, albuminuria, and CKD were prevalent in 8.30%, 12.16%, and 17.68% of people, respectively. SIRI and CKD were shown to be positively correlated in the study (OR = 1.24; 95% CI: 1.19, 1.30). Furthermore, a nonlinear correlation was discovered between SIRI and CKD. SIRI and CKD are both positively correlated on the two sides of the breakpoint (SIRI = 2.04). Moreover, increased SIRI levels were associated with greater prevalences of low-eGFR and albuminuria (albuminuria: OR = 1.27; 95% CI: 1.21, 1.32; low-eGFR: OR = 1.11; 95% CI: 1.05, 1.18). ROC analysis demonstrated that, compared to other inflammatory indices (SII, NHR, LHR, MHR, and PHR), SIRI exhibited superior discriminative ability and accuracy in predicting CKD, albuminuria, and low-eGFR. Discussion: When predicting CKD, albuminuria, and low-eGFR, SIRI may show up as a superior inflammatory biomarker when compared to other inflammatory biomarkers (SII, NHR, LHR, MHR, and PHR). American adults with elevated levels of SIRI, SII, NHR, MHR, and PHR should be attentive to the potential risks to their kidney health.
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Albuminuria , Insuficiencia Renal Crónica , Adulto , Masculino , Humanos , Estados Unidos , Encuestas Nutricionales , Albuminuria/epidemiología , Insuficiencia Renal Crónica/complicaciones , Inflamación/epidemiología , Inflamación/complicaciones , Lipoproteínas HDL , BiomarcadoresRESUMEN
Two-dimensional (2D) materials are an excellent platform for surface-enhanced Raman spectroscopy (SERS). For ReS2, the Raman enhancement effect can be highly improved through the dipole-dipole interactions and synergistic resonance effects in the phase-engineering ReS2 films. However, the performance of the substrate can be improved further through regulating the electronic interaction between the ReS2 and probe molecules. Herein, a dynamic coulomb repulsion strategy is proposed to trigger an electronic state redistribution by asymmetric electrostatic interactions. With the phase-engineering ReS2/graphene heterostructure as a prototype, under laser excitation, the generated hot electrons in graphene and ReS2 can repel each other due to Coulomb interaction, which breaks the symmetrical distribution of hot electrons in ReS2, and increases the electronic concentration at the interface between ReS2 and the probe molecule. With R6G as the probe molecule, the asymmetric electron distribution and synergistic resonance effects on their interface improve the limit of detection to 10-12 M with an EF of 2.15 × 108. Meanwhile, the heterostructure also shows good uniformity, stability as well as unique anisotropy. This strategy can be generalized to other 2D heterostructures to obtain the ultrasensitive SERS substrates.
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BACKGROUND: The psychological state of patients with post stroke limb movement disorders undergoes a series of changes that affect rehabilitation training and recovery of limb motor function. AIM: To determine the correlation between motor rehabilitation and the psychological state of patients with limb movement disorders after stroke. METHODS: Eighty patients with upper and lower limb dysfunction post stroke were retrospectively enrolled in our study. Based on Hospital Anxiety and Depression Scale (HADS) scores measured before rehabilitation, patients with HADS scores ≥ 8 were divided into the psychological group; otherwise, the patients were included in the normal group. Motor function and daily living abilities were compared between the normal and psychological groups. Correlations between the motor function and psychological status of patients, and between daily living ability and psychological status of patients were analyzed. RESULTS: After 1, 2, and 3 wk of rehabilitation, both the Fugl-Meyer assessment and Barthel index scores improved compared to their respective baseline scores (P < 0.05). A greater degree of improvement was observed in the normal group compared to the psychological group (P < 0.05). There was a negative correlation between negative emotions and limb rehabilitation (-0.592 ≤ r ≤ -0.233, P < 0.05), and between negative emotions and daily living ability (-0.395 ≤ r ≤ -0.199, P < 0.05). CONCLUSION: There is a strong correlation between motor rehabilitation and the psychological state of patients with post stroke limb movement disorders. The higher the negative emotions, the worse the rehabilitation effect.
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AIMS: We aimed to investigate the potential association between weight-adjusted-waist index (WWI) and chronic kidney disease (CKD). DESIGN AND METHODS: This research examined data collected from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020. CKD was defined as the low estimated glomerular filtration rate (eGFR) or the existence of albuminuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30mg/g). Low-eGFR was described as eGFR < 60 mL/min/1.73m2. The associations between WWI with CKD, albuminuria, and low-eGFR were examined using generalized additive models and weighted multivariable logistic regression models. We also analyzed the associations of other obesity indicators with CKD, albuminuria, and low-eGFR, including body mass index (BMI), waist-to-height ratio (WHtR), waist circumference(WC), height, and weight. The receiver operating characteristic (ROC) curves were used to assess and compare their diagnostic abilities. RESULTS: Males made up 48.26% of the total 40,421 individuals that were recruited. The prevalences of CKD, albuminuria, and low-eGFR were 16.71%, 10.97%, and 7.63%, respectively. WWI was found to be positively linked with CKD (OR = 1.42; 95% CI: 1.26, 1.60). A nonlinear connection between WWI and CKD was found using smooth curve fitting. Additionally, a higher prevalence of albuminuria is linked to a higher level of WWI (OR = 1.60; 95% CI: 1.40, 1.82). Different stratifications did not substantially influence the connection between WWI and CKD, albuminuria, and low-eGFR, according to subgroup analysis and interaction tests. We observed higher height was related to higher low-eGFR prevalence (OR = 1.05; 95% CI: 1.03, 1.06). ROC analysis revealed that WWI had the best discrimination and accuracy for predicting CKD and albuminuria compared to other obesity indicators (BMI, WHTR, WC, height and weight). In addition, height had the highest area under the curve (AUC) value for predicting low-eGFR. CONCLUSION: WWI is the best obesity indicator to predict CKD and albuminuria compared to other obesity indicators (BMI, WHTR, WC, height, and weight). WWI and CKD and albuminuria were found to be positively correlated. Furthermore, height had the strongest ability to predict low-eGFR. Therefore, the importance of WWI and height in assessing kidney health in US adults should be emphasized.
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Albuminuria , Insuficiencia Renal Crónica , Adulto , Masculino , Humanos , Femenino , Estudios Transversales , Encuestas Nutricionales , Albuminuria/diagnóstico , Albuminuria/epidemiología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Obesidad/diagnóstico , Obesidad/epidemiologíaRESUMEN
Ultrasound has been widely used for physical modifications of starch because of its effectiveness and environment friendliness; however, only a few reports have focused on the effect of varying ultrasonic treatments on the physicochemical properties of potato flour. In the present study, ultrasound at varying power levels (200, 300, 400, 500, and 600 W) and time intervals (20, 40, 60, 80, and 100 min) were used to obtain sonicated flour. Sonicated potato flour exhibited a significant (P < 0.05) decrease in blue value and oil holding capacity but an increase in swelling power, water solubility, syneresis rate, and transparency. Moreover, ultrasound decreased the RDS content while increasing RS and SDS contents. Thermal properties demonstrated significant (P < 0.05) increases in T0 (64.39â-83.52â) and TC (144.29â-146.87â) but a decrease in ΔH of the sonicated flour. SEM revealed wrinkles, less debris, and larger particle size at the surface of the sonicated flour. FTIR profiles of all samples exhibited similar characteristics peaks, but the sonicated flour had a higher R1047/1022 value. Additionally, ultrasound did not affect crystalline patterns, but it increased the crystallinity of the sonicated flour. Our study contributes to the understanding of physicochemical property changes of sonicated potato flour, which could have industrial applications.
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Harina , Almidón , Tamaño de la PartículaRESUMEN
Mitochondrial viscosity is a critical factor affecting numerous physiological processes, including phagocytosis. Abnormal viscosity in mitochondria is related to some pathological activities and diseases. Evaluating and detecting the changes in mitochondrial viscosity in vivo is crucial. Thus, a mitochondria-targeted red-emitting fluorescent probe (VP) was prepared, and can be used to detect viscosity with high selectivity and sensitivity. The synthesis of probe VP was as simple as two steps and the cost was low. In addition, the fluorescence intensity (log I615) exhibited an excellent relationship with viscosity (log η) in the range of 0.5 - 2.5 (R2 = 0.9985) in water/glycerol mixture. It is noteworthy that the probe VP displayed the highest signal-to-noise ratio (about 50-fold) for viscosity in water and glycerol system. The probe VP can visualize the mitochondrial viscosity change in living cells. More importantly, phagocytic test for BV2 cells further demonstrated that phagocytosis decreased with increased viscosity. Furthermore, VP was successfully used for monitoring the mitophagy process induced by starvation, and mitochondrial viscosity exhibited enhancement during mitophagy. The probe was a potential tool for studying viscosity and phagocytosis.
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Glicerol , Imagen Óptica , Humanos , Viscosidad , Células HeLa , Imagen Óptica/métodos , Mitocondrias/patología , Colorantes Fluorescentes , AguaRESUMEN
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDDs) threatening the lives of millions of people worldwide, including especially elderly people. Currently, due to the lack of a timely diagnosis and proper intervention strategy, AD and PD largely remain incurable. Innovative diagnosis and therapy are highly desired. Exosomes are small vesicles that are present in various bodily fluids, which contain proteins, nucleic acids, and active biomolecules, and which play a crucial role especially in intercellular communication. In recent years, the role of exosomes in the pathogenesis, early diagnosis, and treatment of diseases has attracted ascending attention. However, the exact role of exosomes in the pathogenesis and theragnostic of AD and PD has not been fully illustrated. In the present review, we first introduce the biogenesis, components, uptake, and function of exosomes. Then we elaborate on the involvement of exosomes in the pathogenesis of AD and PD. Moreover, the application of exosomes in the diagnosis and therapeutics of AD and PD is also summarized and discussed. Additionally, exosomes serving as drug carriers to deliver medications to the central nervous system are specifically addressed. The potential role of exosomes in AD and PD is explored, discussing their applications in diagnosis and treatment, as well as their current limitations. Given the limitation in the application of exosomes, we also propose future perspectives for better utilizing exosomes in NDDs. Hopefully, it would pave ways for expanding the biological applications of exosomes in fundamental research as well as theranostics of NDDs.
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Enfermedad de Alzheimer , Exosomas , Enfermedad de Parkinson , Humanos , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Exosomas/metabolismo , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Medicina de PrecisiónRESUMEN
Layer 1 (L1) interneurons (INs) participate in various brain functions by gating information flow in the neocortex, but their role in the medial entorhinal cortex (MEC) is still unknown, largely due to scant knowledge of MEC L1 microcircuitry. Using simultaneous triple-octuple whole-cell recordings and morphological reconstructions, we comprehensively depict L1IN networks in the MEC. We identify three morphologically distinct types of L1INs with characteristic electrophysiological properties. We dissect intra- and inter-laminar cell-type-specific microcircuits of L1INs, showing connectivity patterns different from those in the neocortex. Remarkably, motif analysis reveals transitive and clustered features of L1 networks, as well as over-represented trans-laminar motifs. Finally, we demonstrate the dorsoventral gradient of L1IN microcircuits, with dorsal L1 neurogliaform cells receiving fewer intra-laminar inputs but exerting more inhibition on L2 principal neurons. These results thus present a more comprehensive picture of L1IN microcircuitry, which is indispensable for deciphering the function of L1INs in the MEC.
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Corteza Entorrinal , Neocórtex , Corteza Entorrinal/fisiología , Interneuronas/fisiología , Neuronas/fisiología , Fenómenos ElectrofisiológicosRESUMEN
Quinones are potential pollutants and redox active compounds widely distributed in environmental media. In this study, methyl-p-benzoquinone (MBQ) was introduced into Fe(III)/peroxydisulfate system (Fe(III)/PDS) to expedite the conversion of Fe(III) to Fe(II) and the degradation of atrazine (ATZ), ultimately establishing an environmentally friendly system of "treating pollution with pollution". MBQ/Fe(III)/PDS system showed superior performance to traditional Fe(II)/PDS system in pH range of 2-7. Sulfate radical (SO4â¢-) and hydroxyl radical (â¢OH) were confirmed to exist in MBQ/Fe(III)/PDS system according to alcohol quenching experiments and ESR tests. Meanwhile, stable 80% of η[PMSO2] (i.e., the molar ratio of PMSO2 generation to PMSO consumption) was achieved and manifested that highly reactive substance Fe(IV) also participated in MBQ/Fe(III)/PDS system. The spontaneous transformation of MBQ and methyl-hydroquinone (MHQ) drove Fe(III)/Fe(II) cycle, during which MHQ induced Fe(III) reduction and Fe(II) regeneration. Transformation pathways of ATZ were proposed based on HPLC-MS detection and DFT calculation and ATZ degradation could be initiated by lateral chain oxidation and dechlorination-hydroxylation. The acute toxicity, bioaccumulation factor, developmental toxicity and mutagenicity of ATZ and its degradation intermediates were evaluated by Toxicity Estimation Software Tool, and the luminescent bacteria test was conducted to investigate the acute toxicity variation of the reaction solution. Cl- obviously inhibited ATZ degradation and three main by-products generation, while humic acid (HA) had little effect on them probably due to the established balance between inhibition (some components in HA competed to consume reactive species) and acceleration (quinone units in HA also facilitated Fe(III)/Fe(II) cycle).
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Atrazina , Contaminantes Químicos del Agua , Atrazina/química , Compuestos Férricos , Quinonas , Teoría Funcional de la Densidad , Oxidación-Reducción , Compuestos Ferrosos , Contaminantes Químicos del Agua/análisisRESUMEN
In this study, natural pyrite (NP) was used to activate peroxydisulfate (PDS) for imidacloprid (IMD) degradation. NP was characterized by X-ray diffraction (XRD), X-ray fluorescence spectrometry (XRF), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Effects of key reaction parameters (NP dosage, PDS concentration and initial pH) and co-existing ions on IMD degradation in the NP/PDS system were investigated. Quenching experiments and electron spin resonance (ESR) tests identified the existence of sulfate radical (SO4â¢-), hydroxyl radical (â¢OH), singlet oxygen (1O2) and superoxide radical (O2â¢-). The cumulative concentration of SO4â¢- and â¢OH were quantified by the formation of benzoquinone (BQ) and p-hydroxybenzoic acid (HBA), respectively. Meanwhile, more than 60% of methylphenyl sulfoxide (PMSO) was selectively converted to methylphenyl sulfone (PMSO2), revealing that Fe(IV) was dominant in the NP/PDS system. The order of contribution of the three reactive species in the NP/PDS system was Fe(IV) > â¢OH > SO4â¢- (contributions of 1O2 and O2â¢- were negligible). Fe(II) released from NP played a crucial role in PDS activation, and sulfur species in NP could also boost Fe(III)/Fe(II) cycle and contribute to the generation of reactive species. Further, the possible degradation pathways of IMD have been proposed based on the detected intermediates using high-performance liquid chromatography-mass spectrometry (HPLC-MS), and the toxicity (including acute toxicity, developmental toxicity and mutagenicity) of these intermediates have been predicted using Toxicity Estimation Software Tool (T.E.S.T). Moreover, NP/PDS system was applied in four natural water bodies and IMD degradation efficiency reached more than 97% after adjusting the pH to 3. The fluorescence excitation-emission matrix (EEM) spectra showed that in addition to IMD, NP/PDS system could also remove other impurities.
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Compuestos Férricos , Azufre , Oxidación-Reducción , Compuestos FerrososRESUMEN
Aims: This investigation examined the possibility of a relationship between neutrophil-to-lymphocyte ratio (NLR) and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients. Methods: Adults with T2DM who were included in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2020 were the subjects of the current cross-sectional investigation. Low estimated glomerular filtration rate (eGFR) (< 60 mL/min/1.73 m2) or albuminuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g) in T2DM patients were the diagnostic criteria for DKD. Weighted multivariable logistic regression models and generalized additive models were used to investigate the independent relationships between NLR levels with DKD, albuminuria, and low-eGFR. Additionally, we examined the relationships between DKD, albuminuria, and low-eGFR with other inflammatory markers, such as the aggregate index of systemic inflammation (AISI), systemic immune-inflammation index (SII), system inflammation response index (SIRI), and platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR). Their diagnostic capabilities were evaluated and contrasted using receiver operating characteristic (ROC) curves. Results: 44.65% of the 7,153 participants who were recruited for this study were males. DKD, albuminuria, and low-eGFR were prevalent in 31.76%, 23.08%, and 14.55% of cases, respectively. Positive correlations were seen between the NLR with the prevalences of DKD, albuminuria, and low-eGFR. Subgroup analysis and interaction tests revealed that the associations of NLR with DKD, albuminuria, and low-eGFR were not significantly different across populations. In addition, MLR, SII and SIRI showed positive associations with the prevalence of DKD. ROC analysis discovered that when compared to other inflammatory markers (MLR, PLR, SII, SIRI, and AISI), NLR may demonstrate more discriminatory power and accuracy in assessing the risk of DKD, albuminuria, and low-eGFR. Conclusion: Compared to other inflammatory markers (MLR, PLR, SII, SIRI, and AISI), NLR may serve as the more effective potential inflammatory marker for identifying the risk of DKD, albuminuria, and low-eGFR in US T2DM patients. T2DM patients with elevated levels of NLR, MLR, SII, and SIRI should be closely monitored for their potential risk to renal function.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Masculino , Adulto , Humanos , Femenino , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Encuestas Nutricionales , Neutrófilos , Albuminuria/etiología , Linfocitos , Inflamación/complicacionesRESUMEN
Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. However, the detailed mechanism of aGPCR activation remains elusive. Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex with Gq, Gs, Gi, G12 and G13. The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G12 and GPCR/G13 engagements. A comparison of Gq, Gs, Gi, G12 and G13 engagements with GPR110 reveals details of G-protein engagement, including a dividing point at the far end of the alpha helix 5 (αH5) of Gα subunit that separates Gq/Gs engagements from Gi/G12/G13 engagements. This is also where Gq/Gs bind the receptor through both hydrophobic and polar interaction, while Gi/G12/G13 engage receptor mainly through hydrophobic interaction. We further provide physiological evidence of GPR110 activation via stalk peptide. Taken together, our study fills the missing information of GPCR/G-protein engagement and provides a framework for understanding aGPCR activation and GPR110 signaling.
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Proteínas de Unión al GTP , Receptores Acoplados a Proteínas G , Adhesión Celular , Microscopía por Crioelectrón , Proteínas de Unión al GTP/metabolismo , Ligandos , Péptidos/química , Unión Proteica , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
Four new daphnane-type diterpenes named tianchaterpenes C-F (1-4) and six known ones were isolated from Stelleropsis tianschanica. Their structures were elucidated based on chemical and spectral analyses. The comparisons of calculated and experimental electronic circular dichroism (ECD) methods were used to determine the absolute configurations of new compounds. Additionally, compounds 1-10 were evaluated for their cytotoxic activities against HGC-27 cell lines; the results demonstrate that compound 2 had strong cytotoxic activities with IC50 values of 8.8 µM, for which activity was better than that of cisplatin (13.2 ± 0.67 µM).
Asunto(s)
Antineoplásicos Fitogénicos , Antineoplásicos , Diterpenos , Medicamentos Herbarios Chinos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Diterpenos/química , Diterpenos/farmacología , Medicamentos Herbarios Chinos/química , Estructura MolecularRESUMEN
Background: A sharp decline in neural regeneration in patients with Alzheimer's disease (AD) exacerbates the decline of cognition and memory. It is of great significance to screen for innovative drugs that promote endogenous neural regeneration. Cytisine N-methylene-(5,7,4'-trihydroxy)-isoflavone (LY01) is a new compound isolated from the Chinese herbal medicine Sophora alopecuroides with both isoflavone and alkaloid characteristic structures. Its pharmacological effects are worth studying. Objective: This study was designed to determine whether LY01 delays the cognitive and memory decline in the early stage of AD and whether this effect of LY01 is related to promoting neural regeneration. Methods: Eight-week-old 5×Familial Alzheimer's Disease (5×FAD) mice were used as disease models of early AD. Three doses of LY01 administered in two courses (2 and 5 weeks) of treatment were tested. Cognition, memory, and anxiety-like behaviors in mice were evaluated by the Morris water maze, fear conditioning, and open field experiments. Regeneration of neurons in the mouse hippocampus was observed using immunofluorescence staining. The effect of LY01 on cell regeneration was also demonstrated using a series of tests on primary cultured neurons, astrocytes, and neural stem cells (NSCs). In addition, flow cytometry and transcriptome sequencing were carried out to preliminarily explored the mechanisms. Results: We found that LY01 reduced the decline of cognition and memory in the early stage of 5×FAD mice. This effect was related to the proliferation of astrocytes, the proliferation and migration of NSCs, and increases in the number of new cells and neural precursor cells in the dentate gyrus area of 5×FAD mice. This phenomenon could be observed both in 2-week-old female and 5-week-old male LY01-treated 5×FAD mice. The neuronal regeneration induced by LY01 was related to the regulation of the extracellular matrix and associated receptors, and effects on the S phase of the cell cycle. Conclusion: LY01 increases the proliferation of NSCs and astrocytes and the number of neural precursor cells in the hippocampus, resulting in neural regeneration in 5×FAD mice by acting on the extracellular matrix and associated receptors and regulating the S phase of the cell cycle. This provides a new idea for the early intervention and treatment of AD.