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BACKGROUND: Spatial transcriptomics (ST) is advancing our understanding of complex tissues and organisms. However, building a robust clustering algorithm to define spatially coherent regions in a single tissue slice and aligning or integrating multiple tissue slices originating from diverse sources for essential downstream analyses remains challenging. Numerous clustering, alignment, and integration methods have been specifically designed for ST data by leveraging its spatial information. The absence of comprehensive benchmark studies complicates the selection of methods and future method development. RESULTS: In this study, we systematically benchmark a variety of state-of-the-art algorithms with a wide range of real and simulated datasets of varying sizes, technologies, species, and complexity. We analyze the strengths and weaknesses of each method using diverse quantitative and qualitative metrics and analyses, including eight metrics for spatial clustering accuracy and contiguity, uniform manifold approximation and projection visualization, layer-wise and spot-to-spot alignment accuracy, and 3D reconstruction, which are designed to assess method performance as well as data quality. The code used for evaluation is available on our GitHub. Additionally, we provide online notebook tutorials and documentation to facilitate the reproduction of all benchmarking results and to support the study of new methods and new datasets. CONCLUSIONS: Our analyses lead to comprehensive recommendations that cover multiple aspects, helping users to select optimal tools for their specific needs and guide future method development.
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Algoritmos , Benchmarking , Análisis por Conglomerados , Animales , Perfilación de la Expresión Génica/métodos , Transcriptoma , Humanos , Programas Informáticos , Alineación de Secuencia/métodosRESUMEN
To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery (P = 0.031) and age (P < 0.001), both of which were negatively associated. And vaginal mucosa thickness demonstrated no significant correlation with body mass index (BMI) (P = 0.325), times of abortions (P = 0.511), times of gestation (P = 0.101), menstrual cycle (P = 0.533), or types of delivery (P = 0.056); epithelial thickness showed significant associations with age (P < 0.001) and types of delivery (P = 0.017), both of which were negative correlations. Moreover, BMI (P = 0.429), times of abortions (P = 0.764), delivery (P = 0.079), gestation (P = 0.475), and menstrual cycle (P = 0.950) were nonassociated with epithelial thickness; lamina propria thickness displayed a significant correlation only with age (P = 0.002), and there were no obvious correlations observed between lamina propria thickness and BMI (P = 0.374), times of abortion (P = 0.417), delivery (P = 0.053), gestation (P = 0.101), types of delivery (P = 0.132) and menstrual cycle (P = 0.495). Moreover, when the age segmentation was thresholded at 35 and 50 years, both epithelial thickness and vaginal mucosa thickness were significantly correlated with age (P < 0.05). Lamina propria thickness was associated with age when the age threshold was set at 35 years (P = 0.007), whereas it showed no strong link with age when the age threshold was 50 years (P = 0.072). This study has innovatively established percentile reference values for vaginal mucosa thickness based on histopathology, furnishing clinicians with objective evidence of variations in vaginal mucosal thickness to facilitate personalized medical decisions for patients. The findings demonstrated a strong link between vaginal mucosa thickness and age, with epithelium likely playing a predominant role, while the association with lamina propria appeared to be less significant. Further research involving a larger sample size is warranted to elucidate the potential relationship with the lamina propria.
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Membrana Mucosa , Vagina , Humanos , Femenino , Vagina/patología , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Membrana Mucosa/patología , Adulto Joven , Anciano , China , Factores de Edad , Adolescente , Índice de Masa Corporal , Epitelio/patologíaRESUMEN
Structural variants (SVs) significantly contribute to human genome diversity and play a crucial role in precision medicine. Although advancements in single-molecule long-read sequencing offer a groundbreaking resource for SV detection, identifying SV breakpoints and sequences accurately and robustly remains challenging. We introduce VolcanoSV, an innovative hybrid SV detection pipeline that utilizes both a reference genome and local de novo assembly to generate a phased diploid assembly. VolcanoSV uses phased SNPs and unique k-mer similarity analysis, enabling precise haplotype-resolved SV discovery. VolcanoSV is adept at constructing comprehensive genetic maps encompassing SNPs, small indels, and all types of SVs, making it well-suited for human genomics studies. Our extensive experiments demonstrate that VolcanoSV surpasses state-of-the-art assembly-based tools in the detection of insertion and deletion SVs, exhibiting superior recall, precision, F1 scores, and genotype accuracy across a diverse range of datasets, including low-coverage (10x) datasets. VolcanoSV outperforms assembly-based tools in the identification of complex SVs, including translocations, duplications, and inversions, in both simulated and real cancer data. Moreover, VolcanoSV is robust to various evaluation parameters and accurately identifies breakpoints and SV sequences.
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Diploidia , Genoma Humano , Variación Estructural del Genoma , Polimorfismo de Nucleótido Simple , Humanos , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Programas Informáticos , HaplotiposRESUMEN
Although trait and state rumination play a central role in the exacerbation of negative affect, evidence suggests that they are weakly correlated and exert distinct influences on emotional reactivity to stressors. Whether trait and state rumination share a common or exhibit distinct neural substrate remains unclear. In this study, we utilized functional near-infrared spectroscopy (fNIRS) combined with connectome-based predictive modeling (CPM) to identify neural fingerprints associated with trait and state rumination. CPM identified distinctive functional connectivity (FC) profiles that contribute to the prediction of trait rumination, primarily involving FC within the default mode network (DMN) and the dorsal attention network (DAN) as well as FC between the DMN, control network (CN), DAN, and salience network (SN). Conversely, state rumination was predominantly associated with FC between the DMN and CN. Furthermore, the predictive features of trait rumination can be robustly generalized to predict state rumination, and vice versa. In conclusion, this study illuminates the importance of both DMN and non-DMN systems in the emergence and persistence of rumination. While trait rumination was associated with stronger and broader FC than state rumination, the generalizability of the predictive features underscores the presence of shared neural mechanisms between the two forms of rumination. These identified connectivity fingerprints may hold promise as targets for innovative therapeutic interventions aimed at mitigating rumination-related negative affect.
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Conectoma , Red en Modo Predeterminado , Rumiación Cognitiva , Espectroscopía Infrarroja Corta , Humanos , Rumiación Cognitiva/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Red en Modo Predeterminado/fisiología , Red en Modo Predeterminado/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Personalidad/fisiología , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , AdolescenteRESUMEN
To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: "urinal collecting apparatus dominated pattern" (40.3%), "bladder compression dominated pattern" (30.7%), "intermittent catheterization dominated pattern" (19.3%) and "urethral indwelling catheterization dominated pattern" (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.
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Vida Independiente , Traumatismos de la Médula Espinal , Vejiga Urinaria Neurogénica , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Transversales , China/epidemiología , Vejiga Urinaria Neurogénica/terapia , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Neurogénica/fisiopatología , Encuestas y Cuestionarios , Anciano , Adulto Joven , Pueblos del Este de AsiaRESUMEN
BACKGROUND: We investigated the presence of Chlamydia psittaci in poultry and the environment in live poultry wholesale markets in Changsha during 2021-2022 and conducted a phylogenetic analysis to understand its distribution in this market. METHODS: In total, 483 samples were analyzed using real-time polymerase chain reaction and 17 C. psittaci-positive samples using high-throughput sequencing, BLAST similarity, and phylogenetic analysis. RESULTS: Twenty-two out of 483 poultry and environmental samples were positive for C. psittaci (overall positivity rate: 4.55%) with no difference in positivity rates over 12 months. Chlamydia psittaci was detected at 11 sampling points (overall positivity rate: 27.5%), including chicken, duck, and pigeon/chicken/duck/goose shops, with pigeon shops having the highest positivity rate (46.67%). The highest positivity rates were found in sewage (12.5%), poultry fecal (7.43%), cage swab (6.59%), avian pharyngeal/cloacal swab (3.33%), and air (2.29%) samples. The ompA sequences were identified in two strains of C. psittaci, which were determined to bear genotype B using phylogenetic analysis. Thus, during monitoring, C. psittaci genotype B was detected in the poultry and environmental samples from the poultry wholesale market in Changsha. CONCLUSIONS: To address the potential zoonotic threat, C. psittaci monitoring programs in live poultry markets should be enhanced.
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Chlamydophila psittaci , Filogenia , Enfermedades de las Aves de Corral , Aves de Corral , Psitacosis , Animales , Chlamydophila psittaci/genética , Chlamydophila psittaci/aislamiento & purificación , Chlamydophila psittaci/clasificación , China/epidemiología , Psitacosis/microbiología , Psitacosis/veterinaria , Psitacosis/epidemiología , Aves de Corral/microbiología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/epidemiología , Pollos/microbiología , Patos/microbiología , Heces/microbiología , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Currently, different guidelines recommend using different methods to determine whether deduplication is necessary when determining the detection rates of multidrug-resistant organisms (MDROs). However, few studies have investigated the effect of deduplication on MDRO monitoring data. In this study, we aimed to investigate the influence of deduplication on the detection rates of MDROs in different specimens to assess its impact on infection surveillance outcomes. METHODS: Samples were collected from hospitalized patients admitted between January 2022 and December 2022; four types of specimens were collected from key monitored MDROs, including sputum samples, urine samples, blood samples, and bronchoalveolar lavage fluid (BALF) samples. In this study, we compared and analysed the detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Escherichia coli (CRECO), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA) under two conditions: with and without deduplication. RESULTS: When all specimens were included, the detection rates of CRKP, CRAB, CRPA, and MRSA without deduplication (33.52%, 77.24%, 44.56%, and 56.58%, respectively) were significantly greater than those with deduplication (24.78%, 66.25%, 36.24%, and 50.83%, respectively) (all P < 0.05). The detection rates in sputum samples were significantly different between samples without duplication (28.39%, 76.19%, 46.95%, and 70.43%) and those with deduplication (19.99%, 63.00%, 38.05%, and 64.50%) (all P < 0.05). When deduplication was not performed, the rate of detection of CRKP in urine samples reached 30.05%, surpassing the rate observed with deduplication (21.56%) (P < 0.05). In BALF specimens, the detection rates of CRKP and CRPA without deduplication (39.78% and 53.23%, respectively) were greater than those with deduplication (31.62% and 42.20%, respectively) (P < 0.05). In blood samples, deduplication did not have a significant impact on the detection rates of MDROs. CONCLUSION: Deduplication had a significant effect on the detection rates of MDROs in sputum, urine, and BALF samples. Based on these data, we call for the Infection Prevention and Control Organization to align its analysis rules with those of the Bacterial Resistance Surveillance Organization when monitoring MDRO detection rates.
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Infección Hospitalaria , Farmacorresistencia Bacteriana Múltiple , Klebsiella pneumoniae , Esputo , Humanos , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/efectos de los fármacos , Esputo/microbiología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/genética , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/genética , Antibacterianos/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/genética , Líquido del Lavado Bronquioalveolar/microbiología , Carbapenémicos/farmacología , Escherichia coli/aislamiento & purificación , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Monitoreo Epidemiológico , HospitalesRESUMEN
Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C2- or C1-symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies.
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Long-read sequencing offers long contiguous DNA fragments, facilitating diploid genome assembly and structural variant (SV) detection. Efficient and robust algorithms for SV identification are crucial with increasing data availability. Alignment-based methods, favored for their computational efficiency and lower coverage requirements, are prominent. Alternative approaches, relying solely on available reads for de novo genome assembly and employing assembly-based tools for SV detection via comparison to a reference genome, demand significantly more computational resources. However, the lack of comprehensive benchmarking constrains our comprehension and hampers further algorithm development. Here we systematically compare 14 read alignment-based SV calling methods (including 4 deep learning-based methods and 1 hybrid method), and 4 assembly-based SV calling methods, alongside 4 upstream aligners and 7 assemblers. Assembly-based tools excel in detecting large SVs, especially insertions, and exhibit robustness to evaluation parameter changes and coverage fluctuations. Conversely, alignment-based tools demonstrate superior genotyping accuracy at low sequencing coverage (5-10×) and excel in detecting complex SVs, like translocations, inversions, and duplications. Our evaluation provides performance insights, highlighting the absence of a universally superior tool. We furnish guidelines across 31 criteria combinations, aiding users in selecting the most suitable tools for diverse scenarios and offering directions for further method development.
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Algoritmos , Genoma Humano , Humanos , Análisis de Secuencia de ADN/métodos , Diploidia , Benchmarking , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
BACKGROUND: Sacral nerve neuromodulation (SNM) has been considered the optimal second-line treatment for fecal incontinence (FI). However, SNM involves high cost and requires highly skilled operators. Percutaneous tibial nerve stimulation (PTNS) has emerged as an alternative treatment modality for FI, yielding varying clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of PTNS compared to sham electrical stimulation for FI. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies from May 12, 2012 to May 12, 2022. RESULTS: Four randomized controlled studies were included in this review, involving a total of 439 adult patients with FI (300 in the PTNS group and 194 in the sham electrical stimulation group). Our meta-analysis revealed that PTNS demonstrated superior efficacy in reducing weekly episodes of FI compared to the control groups (MD - 1.6, 95% CI - 2.94 to - 0.26, p = 0.02, I2 = 30%). Furthermore, a greater proportion of patients in the PTNS group reported more than a 50% reduction in FI episodes per week (RR 0.73, 95% CI 0.57-0.94, p = 0.02, I2 = 6%). However, no significant differences were observed in any domains of the FI Quality of Life (QoL) and St Mark's incontinence scores (MD - 2.41, 95% CI - 5.1 to 0.27, p = 0.08, I2 = 67%). Importantly, no severe adverse events related to PTNS were reported in any of the participants. CONCLUSIONS: Our meta-analysis revealed that PTNS was more effective than sham stimulation in reducing FI episodes and led to a higher proportion of patients reporting more than a 50% reduction in weekly FI episodes.
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Incontinencia Fecal , Ensayos Clínicos Controlados Aleatorios como Asunto , Nervio Tibial , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Incontinencia Fecal/terapia , Estimulación Eléctrica Transcutánea del Nervio/métodos , Estimulación Eléctrica Transcutánea del Nervio/efectos adversos , Resultado del Tratamiento , Adulto , Femenino , Persona de Mediana Edad , Masculino , Calidad de Vida , AncianoRESUMEN
This study aimed to investigate effects of continuous low-speed biogas agitation on the anaerobic digestion (AD) performance and microbial community of high-solids pig manure (total solids content of 10%). Our results reveal that at a biogas agitation intensity of 1.10 L/g feed VS/d, CH4 production increased by 16.67% compared to the non-agitated condition, the removal efficiency of H2S reached 63.18%, and the abundance of Methanosarcina was the highest. The presence of Hungateiclostridiaceae was associated with H2S concentrations. An increasing biogas agitation intensity led to an elevated pH and a decreased oxidation-reduction potential (ORP). Acetate concentrations, pH, and ORP values indicated changes in H2S concentrations. Sedimentibacter demonstrates the potential to indicate biogas agitation intensity and pH. We demonstrate that continuous low-speed biogas agitation effectively increases CH4 production and reduces H2S concentrations in AD of high-solids pig manure, offering a potential technical pathway for developing AD processes for high-solids pig manure, it also demonstrates that AD process can reduce the risk of pathogen and parasite transmission.
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Reactores Biológicos , Microbiota , Porcinos , Animales , Anaerobiosis , Biocombustibles , Estiércol , MetanoRESUMEN
PURPOSE: The purpose of this study is to identify the associated factors of two types of lichenoid vulvar disease (LVD) and to compare the differences in related factors between the different pathological types of lichenoid vulvar disease (LVD). METHODS: The study conducted at the West China second Hospital of Sichuan University included a total of 1770 patients with biopsy-confirmed vulvar lichen simplex chronicus (VLSC)and vulvar lichen sclerosus(VLS), along with 1209 patients with normal vulvovagina as control. Further pathological subtype analysis was carried out on 163 cases of vulvar lichen simplex chronicus and 51 cases of vulvar lichen sclerosus. In addition, Univariate chi-square test and multivariate logistic regression were used to analyze the lichenoid vulvar disease group and vulvovaginal normal control group. RESULTS: Univariate analysis revealed that there were statistically significant differences (P < 0.05) in factors between the LVD group and the control group, except for living type, sleep habit, history of drinking, and allergic diseases. There was no significant difference in late sleep, spicy diet, and coffee intake in the factors of life and eating habits and the concomitant disease factors. Furthermore, univariate analysis showed that except for eating seafood, humid living environment, residence, caffeinated drinks, hypertension, and vaginitis, there were statistical differences in the related factors of LVSC. CONCLUSION: The incidence about lichenoid vulvar disease is influenced by various factors such as dietary habits, living environment, mental stress, concomitant diseases, hormone levels and so on, and there were no significant differences in these factors between VLS and VLSC except for income, work stress, systemic immune diseases, and menopause.
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Neurodermatitis , Enfermedades de la Vulva , Liquen Escleroso Vulvar , Humanos , Femenino , Neurodermatitis/epidemiología , Estudios de Casos y Controles , Enfermedades de la Vulva/epidemiología , Factores de RiesgoRESUMEN
Mesangial proliferative glomerulonephritis (MsPGN) and its related rat model Thy-1 nephritis (Thy-1N) are associated with C5b-9 deposition and are characterized by proliferation of glomerular mesangial cell (GMC) and expansion of extracellular matrix (ECM) expansion, alongside overexpression of multiple growth factors. Although fibroblast growth factor 1 (FGF1), platelet-derived growth factor alpha (PDGFα), and transforming growth factor beta 1 (TGF-ß1) are well known for their proproliferative and profibrotic roles, the molecular mechanisms responsible for regulating the expression of these growth factors have not been thoroughly elucidated. In this study, we found that sublytic C5b-9 induction of sex-determining region Y-box 9 (SOX9) transactivated FGF1, PDGFα, and TGF-ß1 genes in GMCs, resulting in a significant increase in their mRNA and protein levels. Besides, sublytic C5b-9 induction of activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylated SOX9 at serine 181 and serine 64, which enhanced SOX9's ability to transactivate FGF1, PDGFα, and TGF-ß1 genes in GMCs. Furthermore, we demonstrated that inhibiting ERK1/2 activation or silencing either ERK1/2 or SOX9 gene led to reduced SOX9 phosphorylation, decreased generation of FGF1, PDGFα, and TGF-ß1, and ameliorated glomerular injury in rat Thy-1N. Overall, these findings suggest that expression of FGF1, PDGFα, and TGF-ß1 is promoted by ERK1/2-mediated phosphorylation of SOX9, which may provide a valuable insight into the pathogenesis of MsPGN and offer a potential target for the development of novel treatment strategies for MsPGN.
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Factor 1 de Crecimiento de Fibroblastos , Nefritis , Ratas , Animales , Factor 1 de Crecimiento de Fibroblastos/genética , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Fosforilación , Ratas Sprague-Dawley , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Sistema de Señalización de MAP Quinasas , Nefritis/metabolismo , Serina/metabolismoRESUMEN
We conducted a cross-sectional study using an online questionnaire to investigate the current status of urinary tract infections (UTIs) and the use of clean intermittent catheterization (CIC) in Chinese community-based SCI patients and to explore the risk factors for UTIs in patients using CIC. Our findings suggest that the prevalence of UTIS is higher in Chinese community-based SCI patients compared with patients in medically developed countries. In addition, we found that CIC had the lower incidence of UTIs than urinary indwelling catheter (UIC) and suprapubic catheter (SPC), and that SCI patients with CIC had low rates of use and poor compliance. Further analysis indicated that most of the risk factors for UTIs in CIC patients were associated with irregular use of CIC. Therefore, we call for not only the need to provide stronger caregiver support and financial assistance to improve CIC adherence in Chinese community SCI patients, but also the establishment of a database of Chinese SCI patients in order to enhance the management of bladder emptying methods and further standardize the CIC operation in such patients, thus reducing the risk of UTIs in Chinese community SCI patients.
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Traumatismos de la Médula Espinal , Vejiga Urinaria Neurogénica , Infecciones Urinarias , Humanos , Estudios Transversales , Pueblos del Este de Asia , Vejiga Urinaria Neurogénica/etiología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/terapia , Infecciones Urinarias/etiología , Infecciones Urinarias/complicaciones , Cateterismo/efectos adversosRESUMEN
Purpose: We aimed to evaluate the in vitro antibacterial effects of combination of cefepime/avibactam against carbapenem-resistant Klebsiella pneumonia (CRKP) and explore the resistance mechanism of FEP/AVI. Patients and Methods: This study explored the in vitro antibacterial activities of ceftazidime/avibactam (CAZ/AVI) and cefepime/avibactam (FEP/AVI) against 40 and 76 CRKP clinical isolates. Proteomics and metabolomics were employed to investigate the resistance mechanisms of CRKP to FEP/AVI. Results: FEP/AVI (MIC50/MIC90 0.5/4-64/4 µg/mL, resistance rate 17.1%) showed better antibacterial activity against CRKP than CAZ/AVI (MIC50/MIC90 4/4-128/4 µg/mL, resistance rate 20%) in vitro. Bioinformatics analysis showed that the differentially expressed proteins (DEPs) were enriched in alanine, aspartate and glutamate metabolism, and ribosome. Remarkably, transcriptional and translational activity-related pathways were inhibited in FEP/AVI resistant CRKP. Overlap analysis suggested that H-NS might play an important role in resistance to FEP/AVI in CRKP. The mRNA levels of DEPs-related genes (adhE, gltB, purA, ftsI and hns) showed the same trends as DEPs in FEP/AVI susceptible and resistant strains. FEP/AVI resistant isolates demonstrated stronger biofilm formation capacity than susceptible isolates. Metabolomics results showed that disturbed metabolites were mainly lipids, and adenine was decreased in FEP/AVI resistant CRKP. Conclusion: These results indicated that H-NS, GltB and SpoT may directly or indirectly promote biofilm formation of CRKP and led to FEP/AVI resistance, but inhibited ribosomal function. Our study provides a mechanistic insight into the acquisition of resistance to FEP/AVI in Klebsiella pneumoniae.
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Rat Thy-1 nephritis (Thy-1N) is an experimental model for studying human mesangioproliferative glomerulonephritis (MsPGN), and its pathological features are glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) accumulation. Although we have confirmed that renal lesions of Thy-1N rats are sublytic C5b-9-dependent, and ECM accumulation is related to tissue inhibitor of matrix metalloproteinase (TIMP) inhibiting matrix metalloproteinase (MMP) activity, whether sublytic C5b-9 can induce TIMP production by GMC in Thy-1N rat and the underlying mechanism remains unclear. In the study, we proved that the expressions of TIMP3, krÏppel-like transcription factor 5 (KLF5) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were simultaneously up-regulated both in the renal tissues of Thy-1N rats (in vivo) and in the GMC exposed to sublytic C5b-9 (in vitro). Further mechanism exploration discovered that KLF5 and TRAF6 as two upstream molecules could induce TIMP3 gene transcription through binding to the same region i.e., -1801nt to -1554nt (GGGGAGGGGC) and -228nt to -46nt (GCCCCGCCCC) of TIMP3 promoter. In the process, TRAF6 mediated KLF5 K63-linked ubiquitination at K99 and K100 enhancing KLF5 nuclear localization and binding to TIMP3 promoter, augmenting its gene activation. Furthermore, the experiments in vivo exhibited that silencing KLF5, TRAF6 or TIMP3 gene could markedly lessen renal KLF5 K63-linked ubiquitination or TIMP3 induction, ECM accumulation and other pathological changes of Thy-1N rats. Besides, the positive expressions of above-mentioned these proteins and ECM accumulation and their correlation in the renal tissues of MsPGN patients were also demonstrated. Overall, our findings implicate that KLF5 and TRAF6 play a promoting role in sublytic C5b-9-triggered TIMP3 gene transcription and expression, which might provide a novel mechanistic insight into rat Thy-1N and human MsPGN.
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Células Mesangiales , Nefritis , Humanos , Ratas , Animales , Células Mesangiales/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Nefritis/metabolismo , Ubiquitinación , Metaloproteinasas de la Matriz/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Inhibidor Tisular de Metaloproteinasa-3/genética , Inhibidor Tisular de Metaloproteinasa-3/metabolismoRESUMEN
The effects of heterogenous (anaerobic sludge from treating distillery sewage, ASDS) and homologous (anaerobic sludge from treating swine wastewater, ASSW) inocula on anaerobic digestion and the microbial community in an up-flow anaerobic sludge blanket treating swine wastewater were compared. The highest chemical oxygen demand removal efficiencies with ASDS (84.8%) and ASSW (83.1%) were obtained with an organic loading rate of 15 kg COD/m3/d. For ASSW compared with ASDS, methane production efficiency was 15.3% higher and excess sludge production was 73.0% lower. The abundance of the cellulose hydrolyzing bacterium Clostridium sensu stricto_1 with ASDS (36.1%) was 1.5 times that with ASSW, while that of Methanosarcina with ASSW (22.9%) was > 100 times that with ASDS. ASDS reduced the content of pathogenic bacteria by 88.0%, while ASSW maintained a low level of pathogenic bacteria. ASSW greatly improved the methane production efficiency of wastewater and is more suitable for treating swine wastewater.