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Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque, and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops. The human-specific loops are significantly enriched in enhancer-enhancer interactions, and the regulated genes show human-specific expression changes in the subplate, a transient zone of the developing brain critical for neural circuit formation and plasticity. Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors, which may generate new transcription factor binding sites and chromatin structures in human. Collectively, the presented data highlight the value of comparative 3D genome analyses in dissecting the regulatory mechanisms of brain development and evolution.
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Encéfalo/embriología , Evolución Molecular , Feto/embriología , Genoma , Organogénesis/genética , Animales , Secuencia de Bases , Cromatina/metabolismo , Elementos Transponibles de ADN/genética , Elementos de Facilitación Genéticos/genética , Regulación del Desarrollo de la Expresión Génica , Humanos , Macaca mulatta , Ratones , Especificidad de la Especie , Sintenía/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS: The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS: Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION: Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.
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Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Ratones Noqueados , Receptores Inmunológicos , Transducción de Señal , Animales , Ratones , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/etiología , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Proteínas Similares a la Angiopoyetina/metabolismo , Proteínas Similares a la Angiopoyetina/genética , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Ratones Endogámicos C57BL , Sinapsis/metabolismo , Sinapsis/patología , Sinapsis/efectos de los fármacos , Hormonas Peptídicas/metabolismo , Persona de Mediana Edad , FemeninoRESUMEN
The rapid and selective detection of nitro explosives has become one of the current urgent environmental and safety issues. Fluorescent metal-organic frameworks (MOFs) provide strong support for the development of photoactive materials with excellent sensing performances. In this work, Zn2+ and pyrazinoquinoxaline tetracarboxylic acid with high nitrogen content were selected to construct a MOF structure termed Zn-MOF, which had excellent optical properties. The fluorescence sensing performance of Zn-MOF for nitro explosives was also investigated. The structural advantages of Zn-MOF, such as its porous structure, abundant host-guest interaction sites, and stable framework, ensure the prerequisites for various applications. Zn-MOF is not only capable of responding to a wide range of substrates, such as Fe3+, Cr2O72-, and MnO4-, to achieve fluorescence quenching detection but also able to achieve sensitive fluorescence sensing behavior for nitro explosives. In particular, for trinitrotoluene, the Ksv value can reach 8.72 × 103 M-1. The results show that the introduction of pyrazinoquinoxaline groups into MOFs can be an effective strategy for the preparation of highly efficient fluorescent sensing materials for nitro explosives.
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Considering the molar mass between entanglements to be an intrinsic property of ultra-high molecular weight polyethylene (UHMWPE), the number of entanglements per chain increases with increasing molar mass, correspondingly making the UHMWPE intractable. Herein, we dispersed TiO2 nanoparticles with different characteristics into UHMWPE solutions to disentangle the molecular chains. Compared with the UHMWPE pure solution, the viscosity of the mixture solution declines by 91.22%, and the critical overlap concentration increases from 1 wt% to 1.4 wt%. A rapid precipitation method was utilized to obtain UHMWPE and UHMWPE/TiO2 composites from the solutions. The melting index of UHMWPE/TiO2 is 68.85 mg, which is in sharp contrast to that of UHMWPE which is 0 mg. We characterized the microstructures of UHMWPE/TiO2 nanocomposites using TEM, SAXS, DMA, and DSC. Accordingly, this significant improvement in processability contributed to the reduction of entanglements and a schematic model was proposed to explain the mechanism by which nanoparticles disentangle molecular chains. Simultaneously, the composite demonstrated better mechanical properties than UHMWPE. In summary, we provide a strategy to promote the processability of UHMWPE without sacrificing its outstanding mechanical properties.
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BACKGROUND Prior studies suggest that sedentary behavior is a well-known risk factor for cardiometabolic diseases. However, the longitudinal association between overall siting time and kidney function decline is not known. MATERIAL AND METHODS We performed a nationwide prospective cohort study in individuals aged more than 40 years enrolled in the China Cardiometabolic Disease and Cancer Cohort (4C) study. A total of 132 123 individuals were included in this study. Sitting time was measured with the short version of the International Physical Activity Questionnaire (IPAQ). Kidney function decline was defined as an eGFR <60 mL/min/1.73 m² or more than a 30% decrease in eGFR from baseline. Multivariate Cox proportional hazards regression analyses were conducted to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the relation between kidney function decline and sitting time. RESULTS During a mean follow-up of 3.8 years, 3890 (2.9%) participants experienced kidney function decline. Longer sitting time was significantly associated with the risk of kidney function decline (aHR, 1.136; 95% CI, 1.036-1.247, P=0.007, comparing participants with baseline sitting time in the lowest quartile with those in the highest quartile) after adjustment for potential confounders. CONCLUSIONS Longer sitting time was independently and prospectively associated with a higher risk of kidney function decline. Sedentary behavior might represent a modifiable risk factor for chronic kidney disease (CKD) prevention.
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Insuficiencia Renal Crónica , Conducta Sedentaria , Humanos , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Estudios Prospectivos , Tasa de Filtración Glomerular , Factores de Riesgo , Riñón/fisiología , Progresión de la EnfermedadRESUMEN
Atmospheric dryness events are bound to have a broad and profound impact on the functions and structures of grassland ecosystems. Current research has confirmed that atmospheric dryness is a key moisture constraint that inhibits grassland productivity, yet the risk threshold for atmospheric dryness to initiate ecosystem productivity loss has not been explored. Based on this, we used four terrestrial ecosystem models to simulate gross primary productivity (GPP) data, analyzed the role of vapor pressure deficit (VPD) in regulating interannual variability in Chinese grasslands by focusing on the dependence structure of VPD and GPP, and then constructed a bivariate linkage function to calculate the conditional probability of ecosystem GPP loss under atmospheric dryness, and further analyzed the risk threshold of ecosystem GPP loss triggered by atmospheric dryness. The main results are as follows: we found that (1) the observed and modeled VPD of Chinese grasslands increases rapidly in both historical and future periods. VPD has a strongly negative regulation on ecosystem GPP, and atmospheric dryness is an important moisture constraint that causes deficit and even death to ecosystem GPP. (2) The probability of the enhanced atmospheric dryness that induced GPP decline in Chinese grasslands in the future period increases significantly. (3) When the VPD is higher than 40.07 and 27.65 percentile of the past and future time series, respectively, the risk threshold of slight ecosystem GPP loss can be easily initiated by atmospheric dryness. (4) When the VPD is higher than 82.57 and 65.09 percentile, respectively, the threshold of moderate ecosystem GPP loss can be exceeded by the benchmark probability. (5) The risk threshold of severe ecosystem GPP loss is not initiated by atmospheric dryness in the historical period, and the threshold of severe ecosystem GPP loss can be initiated when the future VPD is higher than 91.92 percentile. In total, a slight atmospheric dryness event is required to initiate a slight ecosystem GPP loss threshold, and a stronger atmospheric dryness event is required to initiate a severe ecosystem GPP loss. Our study enhances the understandings of past and future atmospheric dryness on grassland ecosystems, and strongly suggests that more attention be invested in improving next-generation models of vegetation dynamics processes with respect to the response of mechanisms of ecosystem to atmospheric dryness.
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Ecosistema , Pradera , Ciclo del Carbono , China , ProbabilidadRESUMEN
BACKGROUND: ANGPTL8, an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions. This study aimed to investigate circulating levels of ANGPTL8 and its potential association with the risk of kidney function decline in a cohort study. METHODS: We analysed 2,311 participants aged 40 years old and older from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Kidney function decline was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL per minute per 1.73 m2 of body surface area, a decrease in eGFR of ≥ 30% from baseline, chronic kidney disease (CKD)-related hospitalization or death, or end-stage renal disease. The association between baseline ANGPTL8 levels and kidney function decline was assessed using multivariable-adjusted Cox proportional hazards models, and inverse possibility of treatment weight (IPTW) was utilized to prevent overfitting. RESULTS: There were 136 (5.9%) cases of kidney function decline over a median of 3.8 years of follow-up. We found that serum ANGPTL8 levels at baseline were elevated in individuals with kidney function decline compared to those without kidney function decline during follow-up (718.42 ± 378.17 vs. 522.04 ± 283.07 pg/mL, p < 0.001). Compared with the first quartile, multivariable-adjusted hazard ratio (95% confidence intervals [CIs]) for kidney function decline was 2.59 (95% CI, 1.41-4.77) for the fourth ANGPTL8 quartile. Furthermore, compared with patients in the first ANGPTL8 quartile, those in the fourth ANGPTL8 quartile were more likely to report a higher stage of CKD (relative risk: 1.33; 95% CI, 1.01-1.74). The conclusions of the regression analyses were not altered in the IPTW models. Multivariable-adjusted restricted cubic spline analyses suggested a linear relationship of ANGPTL8 with kidney function decline (p for nonlinear trend = 0.66, p for linear trend < 0.001). CONCLUSIONS: Participants with higher circulating ANGPTL8 levels were at increased risk for kidney function decline, highlighting the importance of future studies addressing the pathophysiological role of ANGPTL8 in CKD.
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Proteína 8 Similar a la Angiopoyetina/sangre , Tasa de Filtración Glomerular , Enfermedades Renales/sangre , Riñón/fisiopatología , Hormonas Peptídicas/sangre , Adulto , Anciano , Biomarcadores/sangre , China/epidemiología , Progresión de la Enfermedad , Femenino , Hospitalización , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/mortalidad , Enfermedades Renales/fisiopatología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: To investigate the thyroid function changes during controlled ovarian hyperstimulation (COH) and ascertain its impact on reproductive outcomes. METHODS: We conducted meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify studies reported changes in thyroid parameters during COH. We analyzed thyroid-stimulating hormone (TSH) levels, free thyroxin (fT4) levels, changes in estrogens (E2), thyroxine-binding globulin (TBG), relative risks (RRs) of clinical pregnancy rate (CPR), live birth rate (LBR), and mean difference (MD) of TSH increment between the miscarriage group and ongoing pregnancy group. RESULTS: This meta-analysis included fifteen individual studies (n = 1665 subjects). At the end of COH, the mean TSH (2.53 mIU/L; 95% CI, 2.19 to 2.88; I2 = 92.9%) exceeded the upper limit (2.5 mIU/L) and remained above the threshold until one month following embryo transfer (ET). Thyroxin decreased from baseline to the end of COH (-0.18 ng/l; 95% CI, -0.35 to 0.00; I2 = 92.2%). The CPR and LBR of patients with TSH exceeding the cutoff after COH were significantly lower than those of patients with TSH below the threshold (CPR: RR, 0.62; 95% CI, 0.47 to 0.82; I2 = 0.0% and LBR: RR, 0.64; 95% CI, 0.44 to 0.92; I2 = 0.0%). The MD of the increment in TSH levels between the miscarriage and ongoing pregnancy groups was 0.40 mIU/L (95% CI, 0.15 to 0.65; I2 = 0.0%). CONCLUSIONS: This meta-analysis shows that TSH increases and fT4 decreases during COH. COH-induced thyroid disorder impairs reproductive outcomes.
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Tasa de Natalidad/tendencias , Fertilización In Vitro/métodos , Síndrome de Hiperestimulación Ovárica/patología , Índice de Embarazo/tendencias , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Glándula Tiroides/fisiopatología , Femenino , Humanos , Síndrome de Hiperestimulación Ovárica/terapia , EmbarazoRESUMEN
In the treatment of breast cancer, decisions on adjuvant treatment reflect individual patient characteristics like age and comorbidity. This study assessed the association between adherence to guidelines for adjuvant treatment and survival while taking into account age at diagnosis and comorbidities. We collected the Charlson comorbidity index at baseline for 2179 women treated for primary breast cancer from 1992 to 2008 who participated in a German retrospective multicenter cohort study. We assessed subsequent adjuvant therapy guideline adherence and survival in relation to baseline comorbidities. Guidelines for adjuvant chemotherapy and radiotherapy were more often violated in patients with higher Charlson score. Patients with higher Charlson scores received chemotherapy and radiotherapy less often and had higher rates of mastectomy. Irrespective of comorbidity (Charlson score 0, 1-2, ≥3), patients with 100% guideline-adherent adjuvant treatment showed better overall and disease-free survival (DFS) compared to patients with guideline violations (GVs). Controlling for age, comorbidity and tumor characteristics, the hazard ratio for at least one GV was 1.65 (95% confidence interval [CI]: 1.33-2.07) for overall survival and 1.84 (95% CI: 1.53-2.22) for DFS. Guideline-adherent treatment was significantly less frequent in comorbid patients, although guideline adherence was strongly associated with improved survival, irrespective of severity, and number of comorbid diseases.
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Neoplasias de la Mama/mortalidad , Adhesión a Directriz/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Comorbilidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) has become an important nosocomial pathogen, causing considerable morbidity and mortality. During the last 20 years, a variety of genotyping methods have been introduced for screening the prevalence of MRSA. In this study, we developed and evaluated an improved approach capillary gel electrophoresis based multilocus variable-number tandem-repeat fingerprinting (CGE/MLVF) for rapid MRSA typing. A total of 42 well-characterized strains and 116 non-repetitive clinical MRSA isolates collected from six hospitals in northeast China between 2009 and 2010 were tested. The results obtained by CGE/MLVF against clinical isolates were compared with traditional MLVF, spa typing, Multilocus sequence typing/ staphylococcal cassette chromosome mec (MLST/SCCmec) and pulse field gel electrophoresis (PFGE). The discriminatory power estimated by Simpson's index of diversity was 0.855 (28 types), 0.855 (28 patterns), 0.623 (11 types), 0.517 (8 types) and 0.854 (28 patterns) for CGE/MLVF, traditional MLVF, spa typing, MLST/SCCmec and PFGE, respectively. All methods tested showed a satisfied concordance in clonal complex level calculated by adjusted Rand's coefficient. CGE/MLVF showed better reproducibility and accuracy than traditional MLVF and PFGE methods. In addition, the CGE/MLVF has potential to produce portable results. In conclusion, CGE/MLVF is a rapid and easy to use MRSA typing method with lower cost, good reproducibility and high discriminatory power for monitoring the outbreak and clonal spread of MRSA isolates.
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ADN Bacteriano/análisis , Staphylococcus aureus Resistente a Meticilina/genética , Reacción en Cadena de la Polimerasa Multiplex , Proteína Estafilocócica A/genética , Dermatoglifia del ADN , Electroforesis Capilar , Electroforesis en Gel de Campo Pulsado , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Tipificación de Secuencias Multilocus , Secuencias Repetidas en Tándem/genéticaRESUMEN
We aim to screen and analyze the ferroptosis inflammation-related hub genes associated with idiopathic pulmonary fibrosis (IPF). The GSE52463 and GSE110147 datasets were obtained from the GEO database and merged. The DEGs were selected by differential analysis and intersected with inflammation-related genes and ferroptosis-related genes to acquire the ferroptosis-related differentially expressed genes (FRDEGs). GO, KEGG, GSEA, and GSVA were performed to investigate the features of FRDEGs. The key module genes were selected by WGCNA and employed to generate the PPI network using Cytoscape. Subsequently, the hub genes were identified using cytoHubba and validated by ROC curves generated by survivalROC. Finally, the correlations of hub genes were analyzed through Spearman and the subtypes of IPF were constructed using ConsensusClusterPlus. A total of 1814 DEGs were screened out and 18 FRDEGs were acquired from the intersection of DEGs, ferroptosis-related genes, and inflammation-related genes. GO and KEGG analysis revealed that FRDEGs were primarily involved in bacterial-origin molecular, response infectious disease, and iron ion transport. GSEA results suggested a predominant association with autoimmune diseases and GSVA identified ten different pathways between PF and control. Through WGCNA, three highly correlated modules were identified and ten key module genes were obtained by intersecting genes in the three modules with FRDEGs. Finally, employing three algorithms within the cytoHubba led to the identification of eight hub genes: CCND1, TP53, STAT3, CTNNB1 CDH1, ESR1, HSP90AA1, and EP300. Eventually, two distinct subtypes of IPF were identified. The present research successfully identified the hub genes associated with ferroptosis and inflammation and their biological effects on IPF. Furthermore, two disease subtypes of IPF were constructed.
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Chlorine is widely used for sterilization and disinfection of water, but the presence of excess residual chlorine in water poses a substantial threat to human health. At present, there is no portable device which can achieve accurate, rapid, low-cost, and convenient detection of residual chlorine in water. Therefore, it is necessary to develop a device that can perform accurate, rapid, low-cost, and convenient detection of residual chlorine in water. In this study, a portable residual chlorine detection device was developed. A microfluidic chip was studied to achieve efficient mixing of two-phase flow. This microfluidic chip was used for rapid mixing of reagents in the portable residual chlorine detection device, reducing the consumption of reagents, detection time, and device volume. A deep learning algorithm was proposed for predicting residual chlorine concentration in water, achieving precise detection. Firstly, the microfluidic chip structure for detecting mixed reagents was optimized, and the microfluidic chip was fabricated by a 3D-printing method. Secondly, a deep learning (LS-BP) algorithm was constructed and proposed for predicting residual chlorine concentration in water, which can realize dual-channel signal reading. Thirdly, the corresponding portable residual chlorine detection device was developed, and the detection device was compared with residual chlorine detection devices and methods in other studies. The comparison results indicate that the portable residual chlorine detection device has high detection accuracy, fast detection speed, low cost, and good convenience. The excellent performance of the portable residual chlorine detection device makes it suitable for detecting residual chlorine in drinking water, swimming pool water, aquaculture and other fields.
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Conventional photoresponsive materials have low photon utilization due to irregular distribution of photoactive groups, which severely limits the related real applications. Metal-organic frameworks (MOFs) can modulate the regular arrangement of functional groups to improve the electron transport paths and enhance the photon utilization, which provides strong support for the development of photoactive materials with excellent performance. In this work, one effective strategy for constructing a photoactive MOF had been developed via the utilization of Cd2+ and pyrazinoquinoxaline tetracarboxylic acid. The structural advantages of the Cd-MOF, such as a porous structure, abundant subject-object interaction sites, and a stable framework, ensure the prerequisite for various applications, while the better synergistic effect of Cd3 clusters and the pyrazinoquinoxaline derivative ensures efficient electron transfer efficiency. Therefore, by virtue of these structural advantages, the Cd-MOF can achieve fluorescence quenching detection for a variety of substrates, such as Fe3+, Cr2O72-, MnO4-, nitrofuran antibiotics, and TNP explosives, while fluorescence enhancement detection can be achieved for halogen ions, Cs+, Pb2+, and NO2-. In addition, the Cd-MOF can be used as a photocatalyst to successfully achieve the photocatalytic conversion of benzylamine to N-benzylbenzimidate under mild conditions. Thus, the Cd-MOF as a whole shows the possibility of application as a diverse fluorescence detection and photocatalyst and also illustrates the feasibility of preparing high-performance photoactive materials using the pyrazinoquinoxaline derivative.
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Muscle tissue engineering is a promising therapeutic strategy for volumetric muscle loss (VML). Among them, decellularized extracellular matrix (dECM) biological scaffolds have shown certain effects in restoring muscle function. However, researchers have inconsistent or even contradictory results on whether dECM biological scaffolds can efficiently regenerate muscle fibers and restore muscle function. This suggests that therapeutic strategies based on dECM biological scaffolds need to be further optimized and developed. In this study, we used a recellularization method of perfusing adipose-derived stem cells (ASCs) and L6 into adipose dECM (adECM) through vascular pedicles. On one hand, this strategy ensures sufficient quantity and uniform distribution of seeded cells inside scaffold. On the other hand, auxiliary L6 cells addresses the issue of low myogenic differentiation efficiency of ASCs. Subsequently, the treatment of VML animal experiments showed that the combined recellularization strategy can improve muscle regeneration and angiogenesis than the single ASCs recellularization strategy, and the TA of former had greater muscle contraction strength. Further single-nucleus RNA sequencing (snRNA-seq) analysis found that L6 cells induced ASCs transform into a new subpopulation of cells highly expressing Mki67, CD34 and CDK1 genes, which had stronger ability of oriented myogenic differentiation. This study demonstrates that co-seeding ASCs and L6 cells through vascular pedicles is a promising recellularization strategy for adECM biological scaffolds, and the engineered muscle tissue constructed based on this has significant therapeutic effects on VML. Overall, this study provides a new paradigm for optimizing and developing dECM-based therapeutic strategies.
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Matriz Extracelular Descelularizada , Enfermedades Musculares , Animales , Matriz Extracelular , Regeneración , Ingeniería de Tejidos/métodos , Células Madre , Obesidad , Músculo Esquelético/fisiología , Andamios del TejidoRESUMEN
Understanding the cellular and genetic mechanisms driving human-specific features of cortical development remains a challenge. We generated a cell-type resolved atlas of transcriptome and chromatin accessibility in the developing macaque and mouse prefrontal cortex (PFC). Comparing with published human data, our findings demonstrate that although the cortex cellular composition is overall conserved across species, progenitor cells show significant evolutionary divergence in cellular properties. Specifically, human neural progenitors exhibit extensive transcriptional rewiring in growth factor and extracellular matrix (ECM) pathways. Expression of the human-specific progenitor marker ITGA2 in the fetal mouse cortex increases the progenitor proliferation and the proportion of upper-layer neurons. These transcriptional divergences are primarily driven by altered activity in the distal regulatory elements. The chromatin regions with human-gained accessibility are enriched with human-specific sequence changes and polymorphisms linked to intelligence and neuropsychiatric disorders. Our results identify evolutionary changes in neural progenitors and putative gene regulatory mechanisms shaping primate brain evolution.
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Regulatory T (Treg) cells play a critical regulatory role in the immune system by suppressing excessive immune responses and maintaining immune balance. The effective migration of Treg cells is crucial for controlling the development and progression of inflammatory diseases. However, the mechanisms responsible for directing Treg cells into the inflammatory tissue remain incompletely elucidated. In this study, we identified BAF60b, a subunit of switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complexes, as a positive regulator of Treg cell migration that inhibits the progression of inflammation in experimental autoimmune encephalomyelitis (EAE) and colitis animal models. Mechanistically, transcriptome and genome-wide chromatin-landscaped analyses demonstrated that BAF60b interacts with the transcription factor RUNX1 to promote the expression of CCR9 on Treg cells, which in turn affects their ability to migrate to inflammatory tissues. Our work provides insights into the essential role of BAF60b in regulating Treg cell migration and its impact on inflammatory diseases.
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Movimiento Celular , Inflamación , Ratones Endogámicos C57BL , Linfocitos T Reguladores , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Animales , Ratones , Inflamación/patología , Inflamación/metabolismo , Ensamble y Desensamble de Cromatina , Proteínas Cromosómicas no Histona/metabolismo , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/genética , Humanos , Factores de Transcripción/metabolismo , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Colitis/metabolismo , Colitis/patología , Colitis/inmunología , Colitis/genéticaRESUMEN
BACKGROUND: The optimal drug for treatment with polycystic ovary syndrome (PCOS) was in debate. We did this network meta-analysis to assess the efficacy and safety of different drugs for reducing testosterone levels in women with PCOS. METHODS: We searched studies from inception until January 10, 2023, through PubMed, Embase, and Cochrane Library database. All studies comparing different drugs for reducing testosterone levels in women with polycystic ovary syndrome were included in this network meta-analysis. Outcomes were total testosterone levels, free testosterone levels, and withdraw due to adverse events. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. RESULTS: Finally, a total of 13 studies were finally included in this network meta-analysis. In head-to-head comparison, atorvastatin (WMDâ -3.1, 95% CrI: -3.7 toâ -2.5), metformin (WMDâ -2.6, 95% CrI: -3.5 toâ -1.6), metformin + simvastatin (WMDâ -2.8, 95% CrI: -4.1 toâ -1.5), simvastatin (WMDâ -2.7, 95% CrI: -4.2 toâ -1.3), spironolactone (WMDâ -3.1, 95% CrI: -4.3 toâ -1.9), spironolactone + metformin (WMDâ -3.2, 95% CrI: -4.5 toâ -2.0) were all more effective than the placebo, and the difference was statistically significant (Pâ <â .05). The SUCRA shows that spironolactoneâ +â metformin ranked first (SUCRA, 85.0%), Atorvastatin ranked second (SUCRA, 77.7%), Spironolactone ranked third (SUCRA, 77.2%), and metforminâ +â simvastatin ranked the fourth. The SUCRA of different drugs for free testosterone levels shows that atorvastatin ranked first (SUCRA, 75.0%), spironolactoneâ +â metformin ranked second (SUCRA, 5.3%), metforminâ +â simvastain ranked third (SUCRA, 62.6%), and spironolactone ranked the fourth (SUCRA, 56.4%). No statistically significant differences were found between the 2 treatment groups for withdrawn due to adverse events (Pâ >â .05). CONCLUSIONS: Considering the network meta-analysis and rankings, atorvastatin was recommended to be the optimal drug for treatment PCOS. However, the optimal dose of atorvastatin was unknown and should be verified by more randomized controlled trials.
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Metformina , Síndrome del Ovario Poliquístico , Humanos , Femenino , Espironolactona/uso terapéutico , Atorvastatina/uso terapéutico , Metaanálisis en Red , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Metformina/uso terapéutico , Simvastatina/uso terapéutico , Testosterona/uso terapéuticoRESUMEN
In this work, semi-industrial scale heap leaching of 200 t ion adsorption rare earth ores (IRE-ore) and rare earth elements (REEs) recovery from lixivium was first conducted. Biosynthetic citrate/(Na)3Cit, a typical microbial metabolite, was chosen as the lixiviant to conduct heap leaching. Subsequently, an organic precipitation method was proposed, which used oxalic acid to effectively recover REEs and reduce the production cost by lixiviant regeneration. The results showed that the heap leaching efficiency of REEs reached 98 % with a lixiviant concentration of 50 mmol/L and a solid-liquid ratio of 1:2. The lixiviant can be regenerated during the precipitation process, with REE yields and impurity aluminum yields of 94.5 % and 7.4 %, respectively. The residual solution can then be cyclically used as a new lixiviant after simple adjustment. High-quality rare earth concentrates with a rare earth oxide (REO) content of 96 % can be finally obtained after roasting. This work provides an eco-friendly alternative for IRE-ore extraction to solve the environmental issues caused by traditional technology. The results proved feasibility and provided a foundation for in situ (bio)leaching processes in further industrial tests and production.
RESUMEN
Bioleaching is considered an alternative to traditional rare earth extraction technology. However, since rare earth elements exist as complexes in bioleaching lixivium, they cannot be directly precipitated by normal precipitants, which restricts their further development. This structurally stable complex is also a common challenge in various types of industrial wastewater treatment. In this work, a new method called a three-step precipitation process is first proposed to efficiently recover rare earth-citrate (RE-Cit) complexes from (bio)leaching lixivium. It consists of coordinate bond activation (carboxylation by pH adjustment), structure transformation (Ca2+ addition) and carbonate precipitation (soluble CO32- addition). The optimization conditions are determined to adjust the lixivium pH to around 2.0, then add calcium carbonate until the n(Ca2+): n(Cit3-) is more than 1.4:1 and lastly add sodium carbonate until n(CO32-): n(RE3+) is more than 4:1. The results of precipitation experiments using imitated lixivium show that the rare earth yield is more than 96% and the impurity aluminum yield is less than 20%. Subsequently, pilot tests (1000 L) using real lixivium were successfully conducted. The precipitation mechanism is briefly discussed and proposed by thermogravimetric analysis, Fourier infrared spectroscopy, Raman spectroscopy and UV spectroscopy. This technology is promising in the industrial application of rare earth (bio)hydrometallurgy and wastewater treatment due to its advantages of high efficiency, low cost, environmental friendliness and simple operation.
Asunto(s)
Ácido Cítrico , Metales de Tierras Raras , CitratosRESUMEN
This work aimed to investigate the CO2 gas barrier and mechanical properties of fluorine rubber nanocomposites filled with Ca/Al layered hydroxide (graphene oxide [GO]/LDH-Ca2Al) modified by GO. GO/LDH-Ca2Al nanocomposite fillers were prepared by depositing Ca/Al layered hydroxide (LDH-Ca2Al) into the surface of alkalized GO (Al-GO). The prepared GO/LDH-Ca2Al nanocomposite fillers and complexes were characterized by Fourier infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) for structural and micromorphological characterization. The results showed that GO/LDH-Ca2Al was successfully prepared with strong interactions between Al-GO and LDH, and the compatibility of GO/LDH-Ca2Al nanocomposite fillers with the polymer was significantly improved compared with that of LDH-Ca2Al. Consequently, both the fracture strength (σb) and strain (εb) of GO/LDH-Ca2Al nanocomplexes remarkably increased, and they exhibited excellent mechanical properties. Differential scanning calorimetry and thermogravimetric analysis were used to characterize the thermal stability of GO/LDH-Ca2Al nanocomposite fillers, and GO/LDH-Ca2Al nanocomposite fillers have better thermal stability than LDH-Ca2Al. The reaction products (S-LDH-Ca2Al and S-GO-Ca2Al) of LDH-Ca2Al and GO/LDH-Ca2Al with CO2 were characterized using XRD and TGA, respectively, and the results show that LDH-Ca2Al reacts readily and chemically with CO2, resulting in a lower diffusion coefficient of CO2 in the LDH-Ca2Al nanocomplexes than that of the GO/LDH-Ca2Al nanocomplexes and leading to the destruction of the laminar structure of LDH-Ca2Al, while GO/LDH-Ca2Al has better CO2 resistance stability. GO/LDH-Ca2Al nanocomplexes exhibited a reduced content of hydroxyl groups with pro-CO2 nature exposed on the surface of LDH-Ca2Al, improving the interfacial interaction between the nanofillers and the rubber matrix and enhancing the dispersion of GO/LDH-Ca2Al in the polymers. Moreover, CO2 in the soluble GO/LDH-Ca2Al nanocomposites was significantly reduced, while the diffusion properties demonstrated weak temperature dependence on solubility. The mechanism of the CO2 gas barrier of polymers filled with GO/LDH-Ca2Al was proposed on the basis of the Arrhenius equation.