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OBJECTIVE: To investigate the risk factors of postoperative delirium in elderly patients undergoing spine surgery. METHODS: The basic case data of 566 patients who underwent spine surgery under general anesthesia from January 2021 to January 2023 were retrospectively analyzed. There were 296 males and 270 females with an average age of (71.58 ± 4.21) years old. There were 195 cases of cervical spine surgery, 26 cases of thoracic spine surgery and 345 cases of lumbar spine surgery.According to the occurrence of postoperative delirium, the patients were divided into postoperative delirium group(41 patients) and non-delirium group (525 patients). Univariate analysis was used to analyze the possible influencing factors such as gender, age, weight, smoking history, drinking history, surgical site, preoperative anxiety, intraoperative hypotension times, blood loss and so on, and binary Logistic regression was used to analyze the univariate factors with P<0.05. RESULTS: A total of 41 patients developed postoperative delirium. Univariate analysis showed that age (P=0.000), duration of surgery (P=0.039), preoperative anxiety (P=0.001), blood loss (P=0.000), history of opioid use (P=0.003), history of stroke (P=0.005), C-reactive protein (P=0.000), sodium ion(P=0.000) were significantly different between delirium group and non-delirium group. These factors were included in the binary Logistic regression analysis, and the results showed that age [OR=0.729, 95%CI(0.569, 0.932), P=0.012], opioid use [OR=21.500, 95%CI(1.334, 346.508), P=0.031], blood loss [OR=0.932, 95%CI(0.875, 0.993), P=0.029], C-reactive protein [OR=0.657, 95%CI(0.485, 0.890), P=0.007], preoperative anxiety [OR=23.143, 95%CI(1.859, 288.090), P=0.015], and sodium [OR=1.228, 95%CI(1.032, 1.461), P=0.020] were independent risk factors for the development of delirium after spinal surgery in elderly patients. CONCLUSION: Age, opioid use, blood loss, preoperative anxiety, elevated c-reactive protein, and hyponatremia are independent risk factors for the development of postoperative delirium in elderly patients undergoing spinal surgery.
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Delírio , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Idoso , Fatores de Risco , Delírio/etiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Coluna Vertebral/cirurgia , Idoso de 80 Anos ou mais , Modelos LogísticosRESUMO
ABSTRACT: Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children's Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40-140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1-6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.
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Under the background of comprehensively practicing the overall system concept of the "living community" in the new era, incorporating the carbon neutral development goal into the territorial spatial planning and construction and establishing the territorial spatial pattern and optimization strategy in line with the actual development of Gansu Province are of great significance for promoting the comprehensive green low-carbon transformation and high-quality development of regional economy and society. Taking counties in Gansu Province as an example, based on the perspective of carbon neutrality research, the land use carbon budget of 87 counties in Gansu Province in 2010, 2015, and 2021 was calculated and analyzed. GIS spatial analysis and social network analysis were used to further explore their spatial differentiation characteristics and the overall characteristics of the carbon emission spatial correlation network. At last, combined with the main function zoning, the low-carbon oriented land space optimization zoning was carried out, and differentiated low-carbon development strategies were proposed. The results were as followsï¼ â Carbon emissions in Gansu Province showed an upward trend, but the increase rate decreased, showing a spatial distribution of "high in the central and eastern part of the country, low in the southwest." Construction land was the main carbon source. The carbon uptake showed a spatial distribution of "high in the south and low in the north, high in the west and low in the east." Woodlands were the main carbon sinks. The net carbon emissions showed an increasing trend, and approximately 58.62% of the counties in the province were in a carbon imbalance situation. â¡ In 2021, the spatial network of county carbon emissions was closely related, showing a "core-edge" pattern. The Chenguan District and Qilihe District were in the core position of the network and received more correlation relationships in the network. The network contacts in Longzhong area were frequent, followed by the contacts in Longdongnan area. ⢠Based on carbon emissions, carbon sequestration, and ecological carrying capacity coefficients and using the results of spatial correlation of social networks as role positions, the province was divided into four carbon-neutral sub-districts. At the same time, superimposed analysis of the main function zoning, the county area of the province was reconstructed into seven territorial space zones, and the differentiated regional low-carbon optimization development strategy was proposed for each zone.
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RATIONALE AND OBJECTIVES: to develop a deep learning radiomics graph network (DLRN) that integrates deep learning features extracted from gray scale ultrasonography, radiomics features and clinical features, for distinguishing parotid pleomorphic adenoma (PA) from adenolymphoma (AL) MATERIALS AND METHODS: A total of 287 patients (162 in training cohort, 70 in internal validation cohort and 55 in external validation cohort) from two centers with histologically confirmed PA or AL were enrolled. Deep transfer learning features and radiomics features extracted from gray scale ultrasound images were input to machine learning classifiers including logistic regression (LR), support vector machines (SVM), KNN, RandomForest (RF), ExtraTrees, XGBoost, LightGBM, and MLP to construct deep transfer learning radiomics (DTL) models and Rad models respectively. Deep learning radiomics (DLR) models were constructed by integrating the two features and DLR signatures were generated. Clinical features were further combined with the signatures to develop a DLRN model. The performance of these models was evaluated using receiver operating characteristic (ROC) curve analysis, calibration, decision curve analysis (DCA), and the Hosmer-Lemeshow test. RESULTS: In the internal validation cohort and external validation cohort, comparing to Clinic (AUC=0.767 and 0.777), Rad (AUC=0.841 and 0.748), DTL (AUC=0.740 and 0.825) and DLR (AUC=0.863 and 0.859), the DLRN model showed greatest discriminatory ability (AUC=0.908 and 0.908) showed optimal discriminatory ability. CONCLUSION: The DLRN model built based on gray scale ultrasonography significantly improved the diagnostic performance for benign salivary gland tumors. It can provide clinicians with a non-invasive and accurate diagnostic approach, which holds important clinical significance and value. Ensemble of multiple models helped alleviate overfitting on the small dataset compared to using Resnet50 alone.
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Ghost introgression, or the transfer of genetic material from extinct or unsampled lineages to sampled species, has attracted much attention. However, conclusive evidence for ghost introgression, especially in plant species, remains scarce. Here, we newly assembled chromosome-level genomes for both Carya sinensis and Carya cathayensis, and additionally re-sequenced the whole genomes of 43 C. sinensis individuals as well as 11 individuals representing 11 diploid hickory species. These genomic datasets were used to investigate the reticulation and bifurcation patterns within the genus Carya (Juglandaceae), with a particular focus on the beaked hickory C. sinensis. By combining the D-statistic and BPP methods, we obtained compelling evidence that supports the occurrence of ghost introgression in C. sinensis from an extinct ancestral hickory lineage. This conclusion was reinforced through the phylogenetic network analysis and a genome scan method VolcanoFinder, the latter of which can detect signatures of adaptive introgression from unknown donors. Our results not only dispel certain misconceptions about the phylogenetic history of C. sinensis but also further refine our understanding of Carya's biogeography via divergence estimates. Moreover, the successful integration of the D-statistic and BPP methods demonstrates their efficacy in facilitating a more precise identification of introgression types.
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Introgressão Genética , Genoma de Planta , Filogenia , Genoma de Planta/genética , Genômica , Ásia Oriental , População do Leste AsiáticoRESUMO
Poly (ADP-ribose) polymerase-1 (PARP-1) activity significantly increases during cerebral ischemia/reperfusion. PARP-1 is an NAD+-consumption enzyme. PARP-1 hyperactivity causes intracellular NAD+ deficiency and bioenergetic collapse, contributing to neuronal death. Besides, the powerful trigger of PARP-1 causes the catalyzation of poly (ADP-ribosyl)ation (PARylation), a posttranslational modification of proteins. Here, we found that PARP-1 was activated in the ischemic brain tissue during middle-cerebral-artery occlusion and reperfusion (MCAO/R) for 24 h, and PAR accumulated in the neurons in mice. Using immunoprecipitation, Western blotting, liquid chromatography-mass spectrometry, and 3D-modeling analysis, we revealed that the activation of PARP-1 caused PARylation of hexokinase-1 and lactate dehydrogenase-B, which, therefore, caused the inhibition of these enzyme activities and the resulting cell energy metabolism collapse. PARP-1 inhibition significantly reversed the activity of hexokinase and lactate dehydrogenase, decreased infarct volume, and improved neuronal deficiency. PARP-1 inhibitor combined with pyruvate further alleviated MCAO/R-induced ischemic brain injury in mice. As such, we conclude that PARP-1 inhibitor alleviates neuronal death partly by inhibiting the PARylation of metabolic-related enzymes and reversing metabolism reprogramming during cerebral ischemia/reperfusion injury in mice. PARP-1 inhibitor combined with pyruvate might be a promising therapeutic approach against brain ischemia/reperfusion injury.
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Isquemia Encefálica , Traumatismo por Reperfusão , Camundongos , Animais , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/metabolismo , Poli ADP Ribosilação , Hexoquinase/metabolismo , NAD/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Piruvatos , Lactato Desidrogenases/metabolismoRESUMO
BACKGROUND: Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid-autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual. RESULTS: Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture. CONCLUSIONS: Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.
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Duplicação Gênica , Tetraploidia , Humanos , Alelos , Poliploidia , GenômicaRESUMO
When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes, and its only congeneric species, P. strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics, and the driving forces underneath the incipient speciation of the two Platycarya lineages.
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Carbonato de Cálcio , Juglandaceae , Cálcio , Especiação Genética , GenômicaRESUMO
Resource complementarity can contribute to enhanced ecosystem functioning in diverse plant communities, but the role of facilitation in the enhanced complementarity is poorly understood. Here, we use leaf manganese concentration ([Mn]) as a proxy for rhizosheath carboxylate concentration to explore novel mechanisms of complementarity mediated by phosphorus (P) facilitation. In pot experiments, we showed that mixtures involving Carex korshinskyi, an efficient P-mobilizing species, exhibited greater biomass and relative complementarity effect than combinations without C. korshinskyi on P-deficient soils. Compared with monocultures, leaf [Mn] and [P] of species that are inefficient at P mobilization increased by 27% and 21% when grown with C. korshinskyi (i.e. interspecific P facilitation via carboxylates) rather than next to another inefficient P-mobilizing species. This experimental result was supported by a meta-analysis including a range of efficient P-mobilizing species. Phosphorus facilitation enhanced the relative complementarity effect in low-P environments, related to a greater change in several facilitated species of their root morphological traits relative to those in monoculture. Using leaf [Mn] as a proxy, we highlight a vital mechanism of interspecific P facilitation via belowground processes and provide evidence for the pivotal role of P facilitation mediated by the plasticity of root traits in biodiversity research.
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Ecossistema , Fósforo , Fósforo/metabolismo , Plantas/metabolismo , Biomassa , BiodiversidadeRESUMO
5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone, which causes abnormal urogenital sinus development. The aim of this study was to analyze the relationship between genotype-phenotype, surgical selections, and postoperative complications of 5α-reductase 2-deficient patients with hypospadias. We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children's Hospital, Capital Medical University (Beijing, China), from April 2007 to December 2021. A total of 69 patients were included in this study; the mean age at surgery was 34.1 months, and the average follow-up time was 54.1 months. Sixty children were treated with preoperative hormone stimulation (PHS) to promote penile growth. The average penis length and glans width were increased by 1.46 cm and 0.62 cm, respectively. The most frequent mutations were p.R227Q (39.1%, 54/138), p.Q6* (15.2%, 21/138), p.G203S (12.3%, 17/138), and p.R246Q (11.6%, 16/138). In 64 patients who were followed up, 43 had a one-stage operation and 21 had a staged operation, and there were significant differences in external masculinization score (EMS) ( P = 0.008) and the average number of operation required to cure ( P < 0.001) between one-stage and staged operations. PHS had a positive effect ( P < 0.001) on penile development. The p.R227Q mutation was associated with higher EMS and less severe hypospadias. One-stage surgery can be selected if conditions permit. The growth and development of children are acceptable in the long term, but penis growth remains unsatisfactory. Long-term complications of hypospadias should be considered during puberty.
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Hipospadia , Masculino , Humanos , Criança , Lactente , Hipospadia/cirurgia , Estudos Retrospectivos , Oxirredutases , Complicações Pós-Operatórias , Estudos de Associação GenéticaRESUMO
When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes and its only congeneric species, Platycarya strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole-genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics and the driving forces underneath the incipient speciation of the two Platycarya lineages.
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Carbonato de Cálcio , Juglandaceae , Ásia Oriental , Cálcio , Especiação Genética , Genômica , Juglandaceae/genética , Juglandaceae/fisiologiaRESUMO
Introduction: The decomposition of plant litter mass is responsible for substantial carbon fluxes and remains a key process regulating nutrient cycling in natural and managed ecosystems. Litter decomposition has been addressed in agricultural monoculture systems, but not in intercropping systems, which produce species-diverse litter mass mixtures. The aim here is to quantify how straw type, the soil environment and their combined effects may influence straw decomposition in widely practiced maize/legume intercropping systems. Methods: Three decomposition experiments were conducted over 341 days within a long-term intercropping field experiment which included two nitrogen (N) addition levels (i.e. no-N and N-addition) and five cropping systems (maize, soybean and peanut monocultures and maize/soybean and maize/peanut intercropping). Experiment I was used to quantify litter quality effects on decomposition; five types of straw (maize, soybean, peanut, maize-soybean and maize-peanut) from two N treatments decomposed in the same maize plot. Experiment II addressed soil environment effects on root decomposition; soybean straw decomposed in different plots (five cropping systems and two N levels). Experiment III addressed 'home' decomposition effects whereby litter mass (straw) was remained to decompose in the plot of origin. The contribution of litter and soil effects to the home-field advantages was compared between experiment III ('home' plot) and I-II ('away' plot). Results and discussions: Straw type affected litter mass loss in the same soil environment (experiment I) and the mass loss values of maize, soybean, peanut, maize-soybean, and maize-peanut straw were 59, 77, 87, 76, and 78%, respectively. Straw type also affected decomposition in the 'home' plot environment (experiment III), with mass loss values of maize, soybean, peanut, maize-soybean and maize-peanut straw of 66, 74, 80, 72, and 76%, respectively. Cropping system did not affect the mass loss of soybean straw (experiment II). Nitrogen-addition significantly increased straw mass loss in experiment III. Decomposition of maize-peanut straw mixtures was enhanced more by 'home-field advantage' effects than that of maize-soybean straw mixtures. There was a synergistic mixing effect of maize-peanut and maize-soybean straw mixture decomposition in both 'home' (experiment III) and 'away' plots (experiment I). Maize-peanut showed greater synergistic effects than maize-soybean in straw mixture decomposition in their 'home' plot (experiment III). These findings are discussed in terms of their important implications for the management of species-diverse straw in food-production intercropping systems.
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In lineages of allopolyploid origin, sets of homoeologous chromosomes may coexist that differ in gene content and syntenic structure. Presence or absence of genes and microsynteny along chromosomal blocks can serve to differentiate subgenomes and to infer phylogenies. We here apply genome-structural data to infer relationships in an ancient allopolyploid lineage, the walnut family (Juglandaceae), by using seven chromosome-level genomes, two of them newly assembled. Microsynteny and gene-content analyses yield identical topologies that place Platycarya with Engelhardia as did a 1980s morphological-cladistic study. DNA-alignment-based topologies here and in numerous earlier studies instead group Platycarya with Carya and Juglans, perhaps misled by past hybridization. All available data support a hybrid origin of Juglandaceae from extinct or unsampled progenitors nested within, or sister to, Myricaceae. Rhoiptelea chiliantha, sister to all other Juglandaceae, contains proportionally more DNA repair genes and appears to evolve at a rate 2.6- to 3.5-times slower than the remaining species.
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Carya , Juglandaceae , Filogenia , Juglandaceae/genética , Genoma , Carya/genética , Reparo do DNA/genéticaRESUMO
To evaluate and compare the outcomes and complications of three different surgical techniques for treating primary proximal hypospadias with ventral curvature (VC) ≥30°, we retrospectively reviewed the medical records of patients who underwent primary repair of proximal hypospadias with VC ≥30° after degloving at Beijing Children's Hospital Affiliated to Capital Medical University (Beijing, China) from January 2019 to January 2021. A total of 152 patients were divided into three groups: transverse preputial island flap (TPIF) combined with Duplay, modified Koyanagi, and staged TPIF, which were performed on 55, 16, and 81 patients, respectively. A total of 39 (25.7%) patients had complications. Complications rates were similar for the TPIF combined with the Duplay group (40.0%) and modified Koyanagi group (50.0%) but lower for the staged TPIF group (11.1%; P < 0.01). The incidence of urethrocutaneous fistulas was significantly higher in TPIF combined with Duplay group (21.8%) compared to staged TPIF group (4.9%; P = 0.01). In univariate analysis, the length of the urethral defect was the single factor that could predict complications; the cutoff was 4.55 cm. More patients in the long urethral defect group than in the short one had complications (34.1% vs 15.7%, P = 0.01). These results indicate that staged TPIF produced a better outcome, whereas more patients in the TPIF combined with Duplay group presented with two or more complications.
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Plant biodiversity-productivity relationships become stronger over time in grasslands, forests, and agroecosystems. Plant shoot and root litter is important in mediating these positive relationships, yet the functional role of plant litter remains overlooked in long-term experiments. We propose that plant litter strengthens biodiversity-ecosystem functioning relationships over time in four ways by providing decomposing detritus that releases nitrogen (N) over time for uptake by existing and succeeding plants, enhancing overall soil fertility, changing soil community composition, and reducing the impact of residue-borne pathogens and pests. We bring new insights into how diversity-productivity relationships may change over time and suggest that the diversification of crop residue retention through increased residue diversity from plant mixtures will improve the sustainability of food production systems.
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Biodiversidade , Ecossistema , Plantas , Nitrogênio , SoloRESUMO
Mesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum stress-inducible secreting protein, has evolutionarily conserved immune-regulatory function that contributes to the negative regulation of inflammation in macrophages. In this study, we investigated the profiles of MANF in the macrophages of the patients with active inflammatory bowel disease (IBD) and the mice with experimental colitis, which was induced in both myeloid cell-specific MANF knockout mice and wild-type mice by 3% dextran sodium sulfate (DSS) for 7 days. We found that MANF expression was significantly increased in intestinal macrophages from both the mice with experimental colitis and patients with active IBD. DSS-induced colitis was exacerbated in myeloid cell-specific MANF knockout mice. Injection of recombinant human MANF (rhMANF, 10 mg·kg-1·d-1, i.v.) from D4 to D6 significantly ameliorated experimental colitis in DSS-treated mice. More importantly, MANF deficiency in myeloid cells resulted in a dramatic increase in the number of Ly6ChiCX3CRint proinflammatory macrophages in colon lamina propria of DSS-treated mice, and the proinflammatory cytokines and chemokines were upregulated as well. Meanwhile, we demonstrated that MANF attenuated Th17-mediated immunopathology by inhibiting BATF2-mediated innate immune response and downregulating CXCL9, CXCL10, CXCL11 and IL-12p40; MANF functioned as a negative regulator in inflammatory macrophages via inhibiting CHOP-BATF2 signaling pathway, thereby protecting against DSS-induced mouse colitis. These results suggest that MANF ameliorates colon injury by negatively regulating inflammatory macrophage transformation, which shed light on a potential therapeutic target for IBD.
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Colite , Doenças Inflamatórias Intestinais , Humanos , Camundongos , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Transdução de Sinais , Macrófagos/metabolismo , Colo/metabolismo , Fatores de Crescimento Neural/genética , Camundongos Knockout , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Receptor 1 de Quimiocina CX3CRESUMO
Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in the salvaging synthesis pathway of the nicotinamide adenine dinucleotide (NAD). Both NAMPT and NAD progressively decline upon aging and neurodegenerative diseases. The depletion of NAMPT induces mitochondrial dysfunction in motor neurons and causes bioenergetic stress in neurons. However, the roles of NAMPT in hippocampus neurons need to be further studied. Using floxed Nampt (Namptflox/flox) mice, we knocked out Nampt specifically in the hippocampus CA1 neurons by injecting rAAV-hSyn-Cre-APRE-pA. The depletion of NAMPT in hippocampus neurons induced cognitive deficiency in mice. Nevertheless, no morphological change of hippocampus neurons was observed with immunofluorescent imaging. Under the transmission electron microscope, we observed mitochondrial swollen and mitochondrial number decreasing in the cell body and the neurites of hippocampus neurons. In addition, we found the intracellular Aß (6E10) increased in the hippocampus CA1 region. The intensity of Aß42 remained unchanged, but it tended to aggregate. The GFAP level, an astrocyte marker, and the Iba1 level, a microglia marker, significantly increased in the mouse hippocampus. In the primary cultured rat neurons, NAMPT inhibition by FK866 decreased the NAD level of neurons at > 10-9 M. FK866 dropped the mitochondrial membrane potential in the cell body of neurons at > 10-9 M and in the dendrite of neurons at > 10-8 M. FK866 decreased the number and shortened the length of branches of neurons at > 10-7 M. Together, likely due to the injury of mitochondria, the decline of NAMPT level can be a critical risk factor for neurodegeneration.
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Hipocampo , Mitocôndrias , Nicotinamida Fosforribosiltransferase , Animais , Camundongos , Ratos , Citocinas/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Homeostase , Mitocôndrias/metabolismo , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismoRESUMO
Based on the PSR model, we built an evaluation system for resource and environment carrying capacity. We used the entropy weight method, the comprehensive index model and the spatial analysis function of GIS to explore the spatial-temporal dynamic of the resource and environment carrying capacity of the Lanzhou-Xining urban agglomeration, and used the obstacle degree model to identify the obstacle factors. The results showed that resource and environment carrying capacity of the Lanzhou-Xining urban agglomeration from 2005 to 2018 showed a fluctuating upward trend, which was generally at good condition. The coefficient of variation of resource and environment carrying capacity had a fluctuating upward trend, while regional differences were gradually expanding. Spatially, resource and environment carrying capacity presented a "dual-core" structure centered on the main urban areas of Lanzhou and Xining. The high-level areas were mainly concentrated in the Hehuang Valley with Lanzhou and Xining as the center and some surrounding counties, while the low-level areas were distributed in the central and southern regions of the urban agglomeration. Among them, there were spatiotemporal variations of the subsystem index. The pressure index showed a fluctuating and decreasing trend, and spatially showed a decreasing distribution characteristic from Lanzhou and Xining urban areas to the peripheral areas. The state index showed a fluctuating upward trend, and spatially showed the evolution characteristics of high in the east and west wings and low in the middle. The response index showed an upward trend, and spatially showed distribution patterns high in the east and middle, and low in the west and outside. The urbanization rate, per capita industrial wastewater discharge, domestic waste harmless treatment rate, water consumption index, and the proportion of environmental protection investment in GDP are the main obstacles restricting the improvement of resource and environment carrying capacity of Lanhzhou-Xining urban agglomeration.
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Conservação dos Recursos Naturais , Rios , China , Cidades , Desenvolvimento Econômico , Urbanização , Águas ResiduáriasRESUMO
BACKGROUND: Persian walnut, Juglans regia, occurs naturally from Greece to western China, while its closest relative, the iron walnut, Juglans sigillata, is endemic in southwest China; both species are cultivated for their nuts and wood. Here, we infer their demographic histories and the time and direction of possible hybridization and introgression between them. RESULTS: We use whole-genome resequencing data, different population-genetic approaches (PSMC and GONE), and isolation-with-migration models (IMa3) on individuals from Europe, Iran, Kazakhstan, Pakistan, and China. IMa3 analyses indicate that the two species diverged from each other by 0.85 million years ago, with unidirectional gene flow from eastern J. regia and its ancestor into J. sigillata, including the shell-thickness gene. Within J. regia, a western group, located from Europe to Iran, and an eastern group with individuals from northern China, experienced dramatically declining population sizes about 80 generations ago (roughly 2400 to 4000 years), followed by an expansion at about 40 generations, while J. sigillata had a constant population size from about 100 to 20 generations ago, followed by a rapid decline. CONCLUSIONS: Both J. regia and J. sigillata appear to have suffered sudden population declines during their domestication, suggesting that the bottleneck scenario of plant domestication may well apply in at least some perennial crop species. Introgression from introduced J. regia appears to have played a role in the domestication of J. sigillata.