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The newly identified type VII CRISPR-Cas candidate system uses a CRISPR RNA-guided ribonucleoprotein complex formed by Cas5 and Cas7 proteins to target RNA1. However, the RNA cleavage is executed by a dedicated Cas14 nuclease, which is distinct from the effector nucleases of the other CRISPR-Cas systems. Here we report seven cryo-electron microscopy structures of the Cas14-bound interference complex at different functional states. Cas14, a tetrameric protein in solution, is recruited to the Cas5-Cas7 complex in a target RNA-dependent manner. The N-terminal catalytic domain of Cas14 binds a stretch of the substrate RNA for cleavage, whereas the C-terminal domain is primarily responsible for tethering Cas14 to the Cas5-Cas7 complex. The biochemical cleavage assays corroborate the captured functional conformations, revealing that Cas14 binds to different sites on the Cas5-Cas7 complex to execute individual cleavage events. Notably, a plugged-in arginine of Cas7 sandwiched by a C-shaped clamp of C-terminal domain precisely modulates Cas14 binding. More interestingly, target RNA cleavage is altered by a complementary protospacer flanking sequence at the 5' end, but not at the 3' end. Altogether, our study elucidates critical molecular details underlying the assembly of the interference complex and substrate cleavage in the type VII CRISPR-Cas system, which may help rational engineering of the type VII CRISPR-Cas system for biotechnological applications.
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The transition of mouse embryonic stem cells (ESCs) between serum/LIF and 2i(MEK and GSK3 kinase inhibitor)/LIF culture conditions serves as a valuable model for exploring the mechanisms underlying ground and confused pluripotent states. Regulatory networks comprising core and ancillary pluripotency factors drive the gene expression programs defining stable naïve pluripotency. In our study, we systematically screened factors essential for ESC pluripotency, identifying TEAD2 as an ancillary factor maintaining ground-state pluripotency in 2i/LIF ESCs and facilitating the transition from serum/LIF to 2i/LIF ESCs. TEAD2 exhibits increased binding to chromatin in 2i/LIF ESCs, targeting active chromatin regions to regulate the expression of 2i-specific genes. In addition, TEAD2 facilitates the expression of 2i-specific genes by mediating enhancer-promoter interactions during the serum/LIF to 2i/LIF transition. Notably, deletion of Tead2 results in reduction of a specific set of enhancer-promoter interactions without significantly affecting binding of chromatin architecture proteins, CCCTC-binding factor (CTCF), and Yin Yang 1 (YY1). In summary, our findings highlight a novel prominent role of TEAD2 in orchestrating higher-order chromatin structures of 2i-specific genes to sustain ground-state pluripotency.
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Cromatina , Proteínas de Unión al ADN , Células Madre Pluripotentes , Factores de Transcripción de Dominio TEA , Animales , Ratones , Cromatina/metabolismo , Cromatina/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Elementos de Facilitación Genéticos , Células Madre Embrionarias de Ratones/metabolismo , Células Madre Embrionarias de Ratones/citología , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Regiones Promotoras Genéticas , Factores de Transcripción de Dominio TEA/genética , Factores de Transcripción de Dominio TEA/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genéticaRESUMEN
Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.
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Electrocatalytic nitrogen reduction reaction (NRR) paves a sustainable way to produce NH3 but suffering from the relatively low NH3 yield and poor selectivity. High-performance NRR catalysts and a deep insight into the structure-performance relationship are higher desired. Herein, a molten-salt approach is developed to synthesize tiny CeO2 nanoparticles anchored by ultra-thin MoN nanosheets as advanced catalysts for NRR. Specifically, a considerably high NH3 yield rate of 27.5 µg h-1 mg-1 with 17.2% Faradaic efficiency (FE) can be achieved at -0.3 V vs (RHE) under ambient conditions. Experimental and density functional theory (DFT) calculations further point out that the incorporation of MoN with CeO2 can promotes the enlargement of the electron deficient area of nitrogen vacancy site. The enlarged electron deficient area contributes to the accommodation of lone pair electrons of N2, which dramatically improves the N2 adsorption/activation and the key intermediates (*NNH and *NH3) generation, thus boosting the NRR performance.
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OBJECTIVES: T helper 9 (Th9) cells are recognised for their characteristic expression of the transcription factor PU.1 and production of interleukin-9 (IL-9), which has been implicated in various autoimmune diseases. However, its precise relationship with rheumatoid arthritis (RA) pathogenesis needs to be further clarified. METHODS: The expression levels of PU.1 and IL-9 in patients with RA were determined by ELISA, western blotting (WB) and immunohistochemical staining. PU.1-T cell-conditional knockout (KO) mice, IL-9 KO and IL-9R KO mice were used to establish collagen antibody-induced arthritis (CAIA), respectively. The inhibitor of PU.1 and IL-9 blocking antibody was used in collagen-induced arthritis (CIA). In an in vitro study, the effects of IL-9 were investigated using siRNAs and IL-9 recombinant proteins. Finally, the underlying mechanisms were further investigated by luciferase reporter analysis, WB and Chip-qPCR. RESULTS: The upregulation of IL-9 expression in patients with RA exhibited a positive correlation with clinical markers. Using CAIA and CIA model, we demonstrated that interventions targeting PU.1 and IL-9 substantially mitigated the inflammatory phenotype. Furthermore, in vitro assays provided the proinflammatory role of IL-9, particularly in the hyperactivation of macrophages and fibroblast-like synoviocytes. Mechanistically, we uncovered that PU.1 and IL-9 form a positive feedback loop in RA: (1) PU.1 directly binds to the IL-9 promoter, activating its transcription and (2) Th9-derived IL-9 induces PU.1 via the IL-9R-JAK1/STAT3 pathway. CONCLUSIONS: These results support that the PU.1-IL-9 axis forms a positive loop in Th9 dysregulation of RA. Targeting this signalling axis presents a potential target approach for treating RA.
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OBJECTIVES: The prevention of mother-to-child transmission of HIV has been a global success. But little is known about the growth parameters of infants delivered by mothers with HIV or the drug resistance of infants with HIV in China. The study aimed to assess growth parameters and drug resistance in Chinese infants exposed to HIV. METHODS: We conducted an 18-month longitudinal follow-up study of 3283 infants (3222 without HIV; 61 with HIV) born to mothers with HIV in the Guangxi Zhuang Autonomous Region between January 2015 and December 2021. The weight and length of all participants was recorded. In addition, genetic subtypes and drug resistance analysis were performed for infants with HIV. RESULTS: Compared with infants without HIV, those with HIV had significantly lower weight/length Z-scores, except at 18 months of age. The length/age Z-scores of infants with HIV was significantly reduced, except at 1 month of age. The weight/age Z-scores of infants with HIV were significantly lower at all follow-up time points. The weight/length Z-scores of male infants without HIV were significantly lower than for female infants without HIV at all follow-up time points. Male infants without HIV had lower length/age and weight/age Z-scores than female infants at the remaining follow-up points, except at 1 month of age. Of a total of 61 infants with HIV, subtype and drug-resistance data were obtained from 37 (60.66%) samples. Infants with HIV were dominated by the CRF01_AE genotype and showed a diversity of mutation sites dominated by non-nucleoside reverse transcriptase inhibitor resistance. CONCLUSION: Our study demonstrates the growth of infants exposed to HIV in southwest China and provides detailed information on subtype distribution and drug resistance of those with HIV. Nutritional support and drug-resistance surveillance for infants exposed to HIV need to be strengthened.
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Farmacorresistencia Viral , Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , China/epidemiología , Lactante , Masculino , Estudios Longitudinales , Estudios de Seguimiento , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Farmacorresistencia Viral/genética , Embarazo , Recién Nacido , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Peso Corporal , GenotipoRESUMEN
OBJECTIVE: To assess and compare the composition of tongue coating microbiota among patients at different stages of rheumatoid arthritis (RA). METHODS: A total of 47 patients diagnosed with RA, as per the American College of Rheumatology criteria, and 10 healthy individuals were enrolled in this study. The RA patients were stratified considering their Disease Activity Score 28 (DAS28), a composite measure based on the 28 tender and swollen joint count and erythrocyte sedimentation rate (ESR). The study population was further categorized into active phase group (LMH group) and inactive phase group (RE group) according to their DAS28 values. DNA extraction was extracted from tongue coating samples. Subsequently, the V3-V4 16S rDNA region was selectively amplified and sequenced through high-throughput 16S rDNA analysis. The resulting data were then utilized to ascertain the microbial contents. RESULTS: Significant variations were observed in the tongue coating microbiota of patients with RA during active and inactive phases, in comparison to healthy individuals (p < 0.05). At the genus level, the presence of Prevotellan, Veillonella, Rothia, and Neisseria in RA patients was notably more evident than in the healthy control (HC) group. These disparities find support in existing research on gut and oral microbiota. During the active phase of RA, the relative abundance of Veillonella, Rothia, and Neisseria in the tongue coating microbiota of patients was significantly higher than in those with inactive RA. These findings underscore the need for further and in-depth research on the potential impact of these microorganisms on the progression of RA disease. CONCLUSION: The results substantiate the hypothesis that tongue coating microbes actively contribute to the progression of RA.
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Artritis Reumatoide , Bacterias , Progresión de la Enfermedad , Microbiota , ARN Ribosómico 16S , Lengua , Humanos , Artritis Reumatoide/microbiología , Lengua/microbiología , Lengua/patología , Femenino , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Adulto , Microbiota/genética , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , ADN Bacteriano/genética , Anciano , Índice de Severidad de la EnfermedadRESUMEN
Cordycepin (COR), a pure compound of Cordyceps, is known as an adenosine analog that exerts many beneficial effects on human health. The steroidogenesis mediated by ovarian granulosa cells is pivotal in maintaining normal female reproductive function. The steroidogenic acute regulatory protein (StAR) regulates the rate-limiting step in steroidogenesis. COR has been shown to stimulate StAR expression in mouse Leydig cells, the steroidogenic cells in the testes. However, the effect of COR on StAR expression in ovarian granulosa cells remains undetermined. In the present study, we show that treatment with COR downregulates StAR expression in a steroidogenic human granulosa-like tumor cell line, KGN, and primary culture of human granulosa-lutein (hGL) cells obtained from patients undergoing in vitro fertilization. Using specific adenosine receptor (AR) antagonists, our results reveal that the inhibitory effect of COR on StAR expression is mediated by AR-A1, -A2A, and -A3. In both KGN and primary hGL cells, COR activates ERK1/2 and AKT signaling pathways, but only activation of ERK1/2 is required for the COR-induced downregulation of StAR expression. In addition, our results demonstrate that COR downregulates StAR expression by reducing the expression of the SP1 transcription factor. These results provide a better understanding of the biological function of COR on StAR expression in the ovary, which may lead to the development of alternative therapeutic approaches for female reproductive disorders.
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Platelet-rich plasma (PRP) has significant potential for various applications and holds clinical value in regenerative medicine. Cryopreservation is used to extend the preservation period of PRP, facilitating its clinical application. However, the potential negative effects of long-term cryopreservation on platelet storage lesion are still uncertain. In this study, PRP was stored at - 30 °C or - 80 °C. Platelet count, apoptosis, reactive oxygen species (ROS) content, and CD62P expression were assessed on the 14th and 28th days. The study also evaluated platelet mitochondria morphology and function, serotonin (5-HT) secretion by platelets, and the inflammatory activating effect of cryopreserved platelets in PRP. The results showed that there were no significant differences in platelet count, the content of 5-HT, and inflammatory effects between fresh PRP and PRP cryopreserved at both - 30 °C and - 80 °C. However, there was an increase in ROS level, apoptosis, and CD62P level after cryopreservation at both temperatures. Additionally, the levels of ROS, apoptosis, and CD62P in platelets were similar after storage at - 30 °C and - 80 °C. The main difference observed was that the morphology and function of mitochondria were severely damaged after storage at - 30 °C, while they were less affected at - 80 °C. Based on these findings, it can be concluded that storing PRP at - 80 °C is more suitable for achieving a better therapeutic effect in clinical applications, but cryopreservation could not replace the current standard.
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Plasma Rico en Plaquetas , Serotonina , Humanos , Especies Reactivas de Oxígeno , Serotonina/metabolismo , Serotonina/farmacología , Conservación de la Sangre/métodos , Plaquetas/metabolismo , Criopreservación/métodosRESUMEN
BACKGROUND: Exploring predictive biomarkers and therapeutic strategies of ICBs has become an urgent need in clinical practice. Increasing evidence has shown that ARID1A deficiency might play a critical role in sculpting tumor environments in various tumors and might be used as pan-cancer biomarkers for immunotherapy outcomes. The current study aims to explored the immune-modulating role of ARID1A deficiency in Hepatitis B virus (HBV) related hepatocellular carcinoma (HBV-HCC) and its potential immunotherapeutic implications. METHODS: In the current study, we performed a comprehensive analysis using bioinformatics approaches and pre-clinical experiments to evaluate the ARID1A regulatory role on the biological behavior, and immune landscape of Hepatitis B virus (HBV) related hepatocellular carcinoma (HBV-HCC). A total of 425 HBV-related hepatocellular carcinoma patients from TCGA-LIHC, AMC and CHCC-HBV cohort were enrolled in bioinformatics analysis. Immunohistochemical staining of HBV-HCC specimens and ARID1A deficiency cellular models were used to validate the results of the analysis. RESULTS: Our results have shown that ARID1A deficiency promoted tumor proliferation and metastasis. More importantly, ARID1A deficiency in HBV-HCC was associated with the higher TMB, elevated immune activity, and up-regulated expression of immune checkpoint proteins, especially TIM-3 in HBV-HCC. Further, the expression of Galectin-9, which is the ligand of TIM-3, was elevated in the ARID1A knockout HBV positive cell line. CONCLUSION: To conclude, we have shown that the ARID1A deficiency was correlated with more active immune signatures and higher expression of immune checkpoints in HBV-HCC. Additionally, the present study provides insights to explore the possibility of the predictive role of ARID1A in HBV-HCC patients responsive to immunotherapy.
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Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Virus de la Hepatitis B/genética , Neoplasias Hepáticas/patología , Receptor 2 Celular del Virus de la Hepatitis A , Biomarcadores de Tumor , Hepatitis B/complicaciones , Proteínas de Unión al ADN , Factores de TranscripciónRESUMEN
Parkinson's disease (PD) is a neurodegenerative disease, the most characteristic pathological feature is the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compactus (SNpc) of the mesencephalon, along with reduced dopamine content in the striatum. Researchers have been searching for drugs and therapies to treat PD in decades. However, no approach could stop the progression of the disease, and even some of them caused adverse clinical side effects. PD has a well-defined lesion. Therefore, it is considered to be one of the most curable central nervous system diseases by cell replacement treatment. Fetal ventral mesencephalic tissue transplantation has been used to treat patients with PD and obtained positive treatment results. However, ethical issues, such as limited donor tissue, and side effects including graft-induced dyskinesias, limit its clinical applications. Neural stem cell (NSC) transplantation is a viable therapy choice because it possesses multipotency, self-renewal ability, and differentiation into DA neurons, which may substitute for lost DA neurons and slow down the neurodegenerative process in PD. Studies that investigated the delivery of NSCs by using animal models of PD revealed survival, migration, and even amelioration of behavioral deficits. Here, the research progress of NSCs or NSC-derived DA neurons in treating PD was reviewed, and the practicability of present manufacturing processes for clinical testing was considered. This review is expected to offer ideas for practical strategies to solve the present technical and biological problems related to the clinical application of NSCs in PD.
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Células-Madre Neurales , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Humanos , Enfermedad de Parkinson/terapia , Neuronas Dopaminérgicas , Trasplante de Células Madre/métodosRESUMEN
BACKGROUND: Little is known about the state of psychological distress of the elderly in China, and research on specific subgroups such as Hakka older adults is almost lacking. This study investigates psychache and associated factors among Hakka elderly in Fujian, China. METHODS: The data analysed in this study were derived from China's Health-Related Quality of Life Survey for Older Adults 2018. The Chinese version of the Psychache Scale (PAS) was used to assess the frequency and intensity of psychache in Hakka older adults. Generalized linear regression analysis was conducted to identify the main socio-demographic factors associated with psychache overall and its frequency and intensity. RESULTS: A total of 1,262 older adults participated, with mean scores of 18.27 ± 6.88 for total PAS, 12.50 ± 4.79 for PAS-Frequency and 5.77 ± 2.34 for PAS-Intensity. On average, females scored higher than males on PAS-Frequency (ß = 0.84, 95% CI = 0.34, 1.35) and PAS-Intensity (ß = 0.48, 95% CI = 0.22, 0.73). Older adults currently living in towns (ß = -2.18, 95% CI = -2.81, -1.54), with their spouse only (ß = -3.71, 95% CI = -4.77, -2.65), or with children (ß = -3.24, 95% CI = -4.26, -2.22) were more likely to score lower on PAS-Frequency. Conversely, older adults who were regular sleepers (ß = -1.19, 95% CI =-1.49, -0.88) or lived with their spouse only (ß = -1.25, 95% CI = -1.78, -0.72) were more likely to score lower on PAS-Intensity. CONCLUSION: Among Hakka elderly, we found a higher frequency and greater intensity of psychache in females, those with poor health status, irregular sleepers, rural residents, solo dwellers, those with below CNY 10,000 in personal savings, and the medically uninsured. The study's findings indicate that policymakers should give more attention to the susceptible population and implement practical interventions to reduce their psychological burden.
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Calidad de Vida , Humanos , Masculino , Femenino , China/epidemiología , Anciano , Anciano de 80 o más Años , Calidad de Vida/psicología , Distrés Psicológico , Persona de Mediana Edad , Factores SexualesRESUMEN
The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Criocirugía , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Criocirugía/métodos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Anciano , Estudios Prospectivos , Adulto , Resultado del Tratamiento , Insuficiencia del TratamientoRESUMEN
BACKGROUND: The relationship between lactate levels and multiple organ dysfunction in patients with severe heatstroke remains unclear. In this study, we aimed to elucidate the clinical significance of lactate in severe heatstroke prognosis and assess whether incorporating lactate in the SOFA score improves its predictive efficacy. METHODS: This study was a multicenter retrospective cohort investigation included 275 patients. Logistic regression analysis was performed to examine the relationship between lactate levels and patient outcomes and complications, including acute kidney injury (AKI), disseminated intravascular coagulation (DIC), and myocardial injury. Further, receiver operating characteristic (ROC) curves and clinical decision curve analysis (DCA) were used to evaluate the predictive power of lactate and SOFA scores in severe heatstroke-associated death. Lastly, the Kaplan-Meier survival curve was employed to differentiate the survival rates among the various patient groups. RESULTS: After adjusting for confounding factors, lactate was demonstrated as an independent risk factor for death (OR = 1.353, 95% CI [1.170, 1.569]), AKI (OR = 1.158, 95% CI [1.007, 1.332]), DIC (OR = 1.426, 95% CI [1.225, 1.659]), and myocardial injury (OR = 2.039, 95% CI [1.553, 2.679]). The area under the curve (AUC) of lactate for predicting death from severe heatstroke was 0.7540, with a cutoff of 3.35. The Kaplan-Meier survival curve analysis showed that patients with elevated lactate levels had higher mortality rates. Additionally, the ROC curves demonstrated that combining lactate with the SOFA score provided better predictive efficacy than the SOFA score alone in patients with severe heatstroke (AUC: 0.9025 vs. 0.8773, DeLong test, P < 0.001). Finally, the DCA curve revealed a higher net clinical benefit rate for lactate combined with the SOFA score. CONCLUSIONS: Lactate is an independent risk factor for severe heatstroke-related death as well as a risk factor for AKI, DIC, and myocardial injury associated with severe heatstroke. Thus, combining lactate with the SOFA score can significantly improve its predictive efficacy in patients with severe heatstroke.
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Lesión Renal Aguda , Sepsis , Humanos , Ácido Láctico , Puntuaciones en la Disfunción de Órganos , Unidades de Cuidados Intensivos , Estudios Retrospectivos , Pronóstico , Curva ROC , Lesión Renal Aguda/etiologíaRESUMEN
BACKGROUND: Ureteropelvic junction obstruction (UPJO) is the most common cause of pediatric congenital hydronephrosis, and continuous kidney function monitoring plays a role in guiding the treatment of UPJO. In this study, we aimed to explore the differentially expressed proteins (DEPs) in the urinary extracellular vesicles(uEVs) of children with UPJO and determine potential biomarkers of uEVs proteins that reflect kidney function changes. METHODS: Preoperative urine samples from 6 unilateral UPJO patients were collected and divided into two groups: differential renal function (DRF) ≥ 40% and DRF < 40%.We subsequently used data-independent acquisition (DIA) to identify and quantify uEVs proteins in urine, screened for DEPs between the two groups, and analyzed biofunctional enrichment information. The proteomic data were evaluated by Western blotting and enzyme-linked immunosorbent assay (ELISA) in a new UPJO testing cohort. RESULTS: After one-way ANOVA, a P adj value < 0.05 (P-value corrected by Benjamin-Hochberg) was taken, and the absolute value of the difference multiple was more than 1.5 as the screening basis for obtaining 334 DEPs. After analyzing the enrichment of the DEPs according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment combined with the protein-protein interaction (PPI) network results, we selected nicotinamide adenine dinucleotide-ubiquinone oxidoreductase core subunit S1 (NDUFS1) for further detection. The expression of NDUFS1 in uEVs was significantly lower in patients with DRF < 40% (1.182 ± 0.437 vs. 1.818 ± 0.489, P < 0.05), and the expression level of NDUFS1 was correlated with the DRF in the affected kidney (r = 0.78, P < 0.05). However, the NDUFS1 concentration in intravesical urine was not necessarily related to the change in DRF (r = 0.28, P = 0.24). CONCLUSIONS: Reduced expression of NDUFS1 in uEVs might indicate the decline of DRF in children with UPJO.
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Biomarcadores , Vesículas Extracelulares , Obstrucción Ureteral , Preescolar , Femenino , Humanos , Masculino , Biomarcadores/orina , Vesículas Extracelulares/metabolismo , Hidronefrosis/orina , Hidronefrosis/congénito , Riñón/metabolismo , Pelvis Renal , Proteómica/métodos , Obstrucción Ureteral/orina , Obstrucción Ureteral/congénitoRESUMEN
OBJECTIVES: Due to the government's liberalization of epidemic control, the current 2019 novel coronavirus disease (COVID-19) has started to spread widely within China. This study aimed to use the fetal heart quantification (fetal HQ) technique to assess the cardiac function and morphology of the fetuses of pregnant women diagnosed with COVID-19 in the early stages of pregnancy. METHODS: Exactly 86 pregnant women diagnosed with COVID-19 infection in early pregnancy (COVID-19 group) and 90 healthy pregnant women (control group) who underwent fetal echocardiography were prospectively included in this study. The fetal HQ technique was applied to compare the differences in the global sphericity index (GSI), global strain values (GS), fractional area change (FAC), and 24-segment fractional shortening (FS) of the left and right ventricles, between the COVID-19 group and the control group. RESULTS: Compared with the control group, the differences in GS and 24-segment FS of the left ventricle in the COVID-19 group were not statistically significant. However, the COVID-19 group showed lower GSI values compared with the control group (1.24 vs 1.28). FAC (48.12%) of the left ventricle and GS (-23.55%), FAC (41.74%) of the right ventricle in the COVID-19 group were reduced compared with FAC (50.50%) of the left ventricle and GS (-27.63%), FAC (46.01%) of the right ventricle in the control group. Segmental analysis revealed reduced FS in segments 20-24 in the COVID-19 group compared with the control group. Right ventricular GS was an independent predictor of adverse pregnancy outcome with an optimal cutoff value of -18.66%. CONCLUSIONS: The results suggest that COVID-19 infection in early pregnancy may have a negative impact on fetal cardiac morphology and function. Fetal HQ may offer a new assessment method for the early identification of fetal cardiac alterations in pregnant women infected with COVID-19.
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COVID-19 , Ecocardiografía , Corazón Fetal , Complicaciones Infecciosas del Embarazo , Ultrasonografía Prenatal , Humanos , Femenino , Embarazo , COVID-19/diagnóstico por imagen , COVID-19/fisiopatología , COVID-19/complicaciones , Corazón Fetal/diagnóstico por imagen , Corazón Fetal/fisiopatología , Adulto , Complicaciones Infecciosas del Embarazo/diagnóstico por imagen , Complicaciones Infecciosas del Embarazo/fisiopatología , Ultrasonografía Prenatal/métodos , Estudios Prospectivos , Ecocardiografía/métodos , SARS-CoV-2 , Sístole , China/epidemiologíaRESUMEN
OBJECTIVE: This study aims to examine the complex nature of opioid use disorder (OUD) in chronic noncancer pain (CNCP) by exploring its antecedents, attributes, consequences, and interrelated concepts. DESIGN: A systematic literature review was conducted to gather relevant studies published between 2015 and 2022, utilizing the CINAHL, MEDLINE, PsycINFO, and PubMed databases. DATA SOURCES: The selected databases provided a comprehensive range of articles related to OUD in CNCP, ensuring a comprehensive topic analysis. METHODS: Twenty-two articles meeting the inclusion criteria were included in the analysis. These articles were critically reviewed and analyzed to identify key themes and concepts related to OUD in CNCP. RESULTS: The findings of this study shed light on the multifaceted aspects of OUD in CNCP, including its antecedents, such as goals of physical function improvement, prescription of opioids for CNCP, social influences, and mental health dynamics. The attributes of OUD in CNCP were identified as chronic pain, noncancer pain, opioid use, misuse, and abuse. OUD's consequences in CNCP include impaired functioning, increased health risks, psychological distress, social challenges, and economic burden. CONCLUSION: Understanding the complexity of OUD in CNCP is crucial for improving patient outcomes. Collaborative efforts among healthcare systems, regulatory bodies, and professional organizations are needed to develop policies promoting safe and effective pain management while mitigating risks associated with opioid use in CNCP. IMPLICATIONS FOR PRACTICE: Implementing policy recommendations derived from this study enhances care and outcomes for individuals with CNCP. By addressing complex issues of OUD in CNCP and adopting evidence-based practices, healthcare providers can optimize pain management and promote well-being in CNCP patients.
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Analgésicos Opioides , Dolor Crónico , Trastornos Relacionados con Opioides , Humanos , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/psicología , Trastornos Relacionados con Opioides/psicología , Trastornos Relacionados con Opioides/complicaciones , Analgésicos Opioides/uso terapéutico , Formación de Concepto , Manejo del Dolor/métodos , Manejo del Dolor/normasRESUMEN
STATEMENT OF PROBLEM: Soft tissue integration helps prevent the bacterial invasion of dental implants, but bibliometric studies on the top 50 most cited articles in the field of soft tissue integration are lacking. PURPOSE: The purpose of this bibliometric study was to analyze the 50 most cited articles since 1999 to explore global trends and research hotspots. MATERIAL AND METHODS: A specific search strategy of the Science Citation Index Expanded (Web of Science) was devised, and relevant article-based, journal-based, and author-based parameters were analyzed. Correlation analysis was performed (α=.05). RESULTS: The number of citations ranged from 71 to 586. Clinical Oral Implants Research was the most cited journal (1722 citations). Berglundh, Tord was the author with the most publications (6 publications) and citations (957 citations). Dental implants and titanium were the keywords with the highest frequency. Switzerland was the country with the highest number of publications (12 publications). Correlation was found between the publication year and average annual citations (P<.001). CONCLUSIONS: This study determined the scientific progress in soft tissue integration. The surface design of dental implant materials is essential for the soft tissue integration of dental implants. Soft tissue integration has been a focus of interest in the past few years, but many experiments still need to be done to improve soft tissue compatibility with innovative materials.
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BACKGROUND: Bacillus velezensis DQA21 is a functional strain used in the fermentation process of strong-aroma baijiu; however, its specific role in the process is still unclear. RESULTS: In this study, specific roles of B. velezensis DQA21 in the fermentation process were explored. Bioaugmentation of B. velezensis DQA21 increased the diversity and abundance of the bacterial community during the first 32 days of fermentation and significantly inhibited the diversity and richness of the fungal community during days 12 to 32. According to cluster analysis, changes in the microbial community structure were observed during fermentation, and the fermentation process could be divided into two stages: stage I, days 0-12; and stage II, days 12-45. Additionally, the microbial community structures during the two fermentation stages were significantly different. Co-occurrence analysis showed that bioaugmentation with Bacillus increased the correlation between microorganisms in jiupei and had a significant impact on the overall network structure of the microbial community. In addition, Bacillus significantly increased the production of flavor substances in jiupei, causing the total esters, total alcohols, and total acids contents to increase by 19.1%, 81.1%, and 25.9% respectively. CONCLUSION: The results suggested that bioaugmentation with B. velezensis DQA21 had a strong impact on the microbial community structure in strong-aroma baijiu, enhancing the volatile flavor components. Additionally, the work also provides a better understanding on the effect of augmentation on the microbial community in jiupei, which could help better regulation of solid-state fermentation in strong-aroma baijiu. © 2024 Society of Chemical Industry.
Asunto(s)
Bacillus , Fermentación , Aromatizantes , Microbiota , Gusto , Bacillus/metabolismo , Aromatizantes/metabolismo , Aromatizantes/química , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Hongos/metabolismo , Odorantes/análisisRESUMEN
CONTEXT: Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP). OBJECTIVE: To explore the effects and mechanisms of action of LWDH in PMOP. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated. RESULTS: LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62. DISCUSSION AND CONCLUSIONS: LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.