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In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.
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Envejecimiento Prematuro , Linfocitos T , Animales , Ratones , Envejecimiento/genética , Envejecimiento Prematuro/genética , Apoptosis , Inflamación , MamíferosRESUMEN
BACKGROUND: The triglyceride-glucose (TyG) index is considered a dependable biomarker for gauging insulin resistance. The atherogenic index of plasma (AIP) represents a marker reflecting atherosclerosis. However, there is currently no study specifically exploring the associations of these two biomarkers with the severity of new-onset coronary artery disease (CAD) under different glucose metabolic states. Therefore, this study aims to evaluate the correlations of these two biomarkers with CAD severity in patients newly diagnosed with CAD under various glucose metabolism conditions. METHOD: Totally 570 subjects first administered coronary angiography were enrolled, including 431 first diagnosed CAD patients and 139 non-CAD patients. CAD severity was gauged by the quantity of narrowed arteries (single-vessel and multi-vessel CAD). According to WHO diabetes guidelines, glucose metabolic states were divided into normal glucose regulation (NGR), pre-diabetes mellitus (Pre-DM), and diabetes mellitus (DM). The relationships of the TyG index and AIP with CAD severity were validated by logistic regression analysis, including adjustment for traditional cardiovascular risk elements and medical treatments. Their predictive efficacy for CAD was evaluated by receiver operating characteristic (ROC) curves. RESULT: The TyG index and AIP were independently correlated with CAD in accordance with logistic regression analysis (both P < 0.05). Regardless of the glucose metabolic states, there was no statistical correlation between the TyG index and CAD severity. However, AIP in NGR patients was significantly related to CAD severity (P < 0.05). The areas under the curve of the TyG index and AIP for predicting CAD were 0.682 and 0.642 (both P < 0.001), respectively, and their optimal cut-off values were 3.210 (Youden index: 0.305) and 0.095 (Youden index:0.246), respectively. CONCLUSION: The TyG index and AIP have significant associations with CAD. The TyG index had no association with CAD severity, regardless of glucose metabolic states. AIP exhibited a discernible link with CAD severity in NGR patients, but not in the pre-DM or DM populations. The TyG index and AIP have similar predictive values for new-onset CAD.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Humanos , Glucosa , Triglicéridos , Glucemia/metabolismo , Factores de Riesgo , Diabetes Mellitus/diagnóstico , BiomarcadoresRESUMEN
BACKGROUND: Remnant cholesterol (RC) represents a low-cost and readily measured lipid index that contributes significantly to residual cardiovascular disease risk. The triglyceride-glucose (TyG) index exhibits a significant correlation with cardiovascular disease occurrence. However, RC and the TyG index have rarely been examined for their potentials in predicting coronary artery disease (CAD). Accordingly, the study was designed to validate the correlations of these two biomarkers with CAD and to compare the forecasted values of these two biomarkers for newly diagnosed CAD. METHODS: Totally 570 subjects firstly administered coronary angiography were enrolled, including 431 newly diagnosed CAD cases and 139 individuals without CAD. The individuals were classified into two groups according to CAD diagnosis. RC was derived as total cholesterol content (mmol/L) - (high density lipoprotein cholesterol content + low density lipoprotein cholesterol content; both in mmol/L). The TyG index was determined as ln (fasting triglyceride level [mg/dL] × fasting plasma glucose level [mg/dL])/2. RESULTS: Baseline feature analysis revealed significant differences in RC and the TyG index between the CAD and non-CAD groups (both P < 0.001). RC and the TyG index were independent risk factors for CAD in accordance with logistic regression analysis (both P < 0.05). Moreover, spearman correlation analysis elucidated CAD had a more remarkable correlation with the TyG index compared with RC (both P < 0.001). Furthermore, according to receiver operating characteristic curve analysis, the TyG index was better than RC in predicting CAD. CONCLUSIONS: The TyG index and RC have significant associations with CAD. Compared with RC, the TyG index possesses a closer correlation with CAD and a higher predictive value for CAD.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Humanos , Glucosa , Estudios Retrospectivos , Triglicéridos , Glucemia/análisis , Enfermedades Cardiovasculares/complicaciones , Factores de Riesgo , Biomarcadores , ColesterolRESUMEN
BACKGROUND: Macrophages are involved in the pathogenesis of pulmonary arterial hypertension (PAH). Caspase-8, an apical component of cell death pathways, is significantly upregulated in macrophages of PAH animal models. However, its role in PAH remains unclear. Caspase-8 plays a critical role in regulating inflammatory responses via inflammasome activation, cell death, and cytokine induction. This study investigated the mechanism of regulation of IL-1ß (interleukin 1ß) activation in macrophages by caspase-8. METHODS: A hypoxia + SU5416-induced PAH mouse model and monocrotaline-induced rat model of PAH were constructed and the role of caspase-8 was analyzed. RESULTS: Caspase-8 and cleaved-caspase-8 were significantly upregulated in the lung tissues of SU5416 and hypoxia-treated PAH mice and monocrotaline-treated rats. Pharmacological inhibition of caspase-8 alleviated PAH compared with wild-type mice, observed as a significant reduction in right ventricular systolic pressure, ratio of right ventricular wall to left ventricular wall plus ventricular septum, pulmonary vascular media thickness, and pulmonary vascular muscularization; caspase-8 ablated mice also showed significant remission. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cellss is closely associated with activation of the NLRP3 (NOD [nucleotide oligomerization domain]-, LRR [leucine-rich repeat]-, and PYD [pyrin domain]-containing protein 3) inflammasome and the IL-1ß signaling pathway. Although caspase-8 did not affect extracellular matrix synthesis, it promoted inflammatory cell infiltration and pulmonary arterial smooth muscle cell proliferation via NLRP3/IL-1ß activation during the development stage of PAH. CONCLUSIONS: Taken together, our study suggests that macrophage-derived IL-1ß via caspase-8-dependent canonical inflammasome is required for macrophages to play a pathogenic role in pulmonary perivascular inflammation.
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Hipertensión Pulmonar , Animales , Caspasa 1/metabolismo , Caspasa 8/metabolismo , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/genética , Hipoxia/complicaciones , Inflamasomas/metabolismo , Inflamación/complicaciones , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Ratones , Monocrotalina/toxicidad , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , RatasRESUMEN
Sea buckthorn (Hippophae rhamnoides), a horticulturally multipurpose species in the family Elaeagnaceae, can build associations with Frankia actinomycetes to enable symbiotic nitrogen-fixing. Currently, no high-quality reference genome is available for an actinorhizal plant, which greatly hinders the study of actinorhizal symbiotic nodulation. Here, by combining short-read, long-read and Hi-C sequencing technologies, we generated a chromosome-level reference genome of H. rhamnoides (scaffold N50: 65 Mb, and genome size: 730 Mb) and predicted 30 812 protein-coding genes mainly on 12 pseudochromosomes. Hippophae rhamnoides was found to share a high proportion of symbiotic nodulation genes with Medicago truncatula, implying a shared molecular mechanism between actinorhizal and rhizobial symbioses. Phylogenetic analysis clustered the three paralogous NODULE INCEPTION (NIN) genes of H. rhamnoides with those of other nodulating species, forming the NIN group that most likely evolved from the ancestral NLP group. The genome of H. rhamnoides will help us to decipher the underlying genetic programming of actinorhizal symbiosis, and our high-quality genome and transcriptomic resources will make H. rhamnoides a new excellent model plant for actinorhizal symbiosis research.
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Frankia , Hippophae , Rhizobium , Frankia/genética , Hippophae/genética , Filogenia , Plantas , Rhizobium/genética , Simbiosis/genéticaRESUMEN
Renal cell carcinoma (RCC) is a frequently diagnosed cancer with high prevalence, which is inversely associated with survival benefit. Although myriad studies have shed light on disease causality, unfortunately, thus far, RCC diagnosis is faced with numerous obstacles partly due to the insufficient knowledge of effective biomarkers, hinting deeper mechanistic understanding are urgently needed. Metabolites are recognized as final proxies for gene-environment interactions and physiological homeostasis as they reflect dynamic processes that are ongoing or have been taken place, and metabolomics may therefore offer a far more productive and cost-effective route to disease discovery, particularly within the arena for new biomarker identification. In this review, we primarily expatiate recent advances in metabolomics that may be amenable to novel biomarkers or therapeutic targets for RCC, which may expand our armaments to win more bettles against RCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Metabolómica , Animales , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Humanos , Neoplasias Renales/patología , Neoplasias Renales/terapiaRESUMEN
BACKGROUND/AIMS: High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines. METHODS: The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied. RESULTS: As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl-2, MMP-2, MMP-8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase-3. MicroRNA (miR)-199a-3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR-199a-3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR-199a-3p. CONCLUSION: HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR-199a-3p, and thereby blockage of mTOR signaling.
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Silenciador del Gen , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Adulto , Anciano , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , ARN Largo no Codificante/genéticaRESUMEN
OBJECTIVE: Liver metastasis, which contributes substantially to high mortality, is the most common recurrent mode of colon carcinoma. Thus, it is necessary to identify genes implicated in metastatic colonization of the liver in colon carcinoma. METHODS: We compared mRNA profiling in 18 normal colon mucosa (N), 20 primary tumors (T) and 19 liver metastases (M) samples from the dataset GSE49355 and GSE62321 of Gene Expression Omnibus (GEO) database. Gene ontology (GO) and pathways of the identified genes were analyzed. Co-expression network and protein-protein interaction (PPI) network were employed to identify the interaction relationship. Survival analyses based on The Cancer Genome Atlas (TCGA) database were used to further screening. Then, the candidate genes were validated by our data. RESULTS: We identified 22 specific genes related to liver metastasis and they were strongly associated with cell migration, adhesion, proliferation and immune response. Simultaneously, the results showed that C-X-C motif chemokine ligand 14 (CXCL14) might be a favorable prediction factor for survival of patients with colon carcinoma. Importantly, our validated data further suggested that lower CXCL14 represented poorer outcome and contributed to metastasis. Gene set enrichment analysis (GSEA) showed that CXCL14 was negatively related to the regulation of stem cell proliferation and epithelial to mesenchymal transition (EMT). CONCLUSIONS: CXCL14 was identified as a crucial anti-metastasis regulator of colon carcinoma for the first time, and might provide novel therapeutic strategies for colon carcinoma patients to improve prognosis and prevent metastasis.
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The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug-target and target-target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.
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Productos Biológicos/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Biología Computacional/métodos , Descubrimiento de Drogas/métodos , Animales , Productos Biológicos/uso terapéutico , Enfermedades Cardiovasculares/enzimología , Dominio Catalítico , Bases de Datos Farmacéuticas , Humanos , Concentración 50 Inhibidora , Modelos MolecularesRESUMEN
Land use competition among economic development, food security and ecological protection posed challenges for the sustainable development in resource-based cities, especially those represented by coal resource-based cities in China. Predicting future land use change under the coupled framework of shared socioeconomic pathways and representative concentration pathways (SSP-RCPs) was a crucial step in devising sustainable development strategies. In this study, the patch-generated land use simulation (PLUS) model coupled with SSP-RCP scenarios (SSP126, SSP245, SSP585) was used to predict land use changes from year 2020 to 2060, identify key management regions for balancing the goals of ecological protection and food security, and propose corresponding measures. The results showed that, (1) the selected driving factors and model parameters effectively simulated land use changes with an Overall accuracy of 0.95, a Kappa coefficient of 0.92, a Figure of Merit of 0.16, an Exchange error ≤5.69 %, a Shift error ≤1.04 %, and a Quantity error ≤0.67 %. (2) All the scenarios, it was observed that the grassland continued to decrease by 0.86 % to 7.34 %, and the forest and built-up land continued to increase, of which forest increased by 2.34 % to 4.03 %, and built-up land increased by 21.02 % to 61.08 %. Cropland only increased in SSP585 scenario, by 4.76 %, but declining by 2.93 % in SSP126 and SSP245 scenario. (3) In future scenarios, the expansion of built-up land has escalated the risk of cropland and grassland loss. Based on the distribution of key land use conversions, four categories of prioritized land management regions and corresponding measures have been proposed. This provided a potential pathway to mitigate risks associated with the protection of cropland and ecological land. Therefore, this study was instrumental in understanding the mechanisms of land use changes in coal resource-based cities, and provided a reference for land use planning.
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BACKGROUND: Data on multiple consecutive health care-associated infections (HAIs) in patients undergoing extracorporeal membrane oxygenation (ECMO) are limited. We aim to identify the characteristics and outcomes of multiple, consecutive HAIs. METHODS: This retrospective study included adult patients who underwent ECMO in a single cardiac ICU in China from May 2015 to December 2022. The incidence, clinical characteristics, risk factors, and impact on in-hospital mortality among patients with non-HAI, single HAI, and multiple HAIs were analyzed. Pathogens and infection sites for each new episode were compared. RESULTS: Of 192 patients, 92 (47.92%) developed 141 separate infections, with 41 (21.35%) experiencing multiple infections during a single ECMO period. Respiratory tract infections (RTIs) constituted the majority (75.89%), and gram-negative bacteria were the predominant pathogens (71.63%). RTIs decreased from 86.9% in the first infection to 14.3% in the third (P < .001), while bloodstream infections increased from 10.9 % to 57.1% (P < .001). The proportion of gram-positive bacteria increased from 9.8% to 42.9% (P = .032). Prolonged ECMO duration was the only independent risk factor for multiple consecutive HAIs (odds ratio (OR)=1.220, P < .001). CONCLUSIONS: Multiple consecutive HAIs during ECMO were frequent, with distinct microbiological changes between initial and subsequent HAIs.
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In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) extracellular vesicles (EVs) have been used as a cell replacement therapy and have been shown to effectively overcome some of the disadvantages of cell therapy. However, the specific mechanism of action of EVs is still unclear, and there is no appropriate system for characterizing the differences in the molecular active substances of EVs produced by cells in different physiological states. We used a data-independent acquisition (DIA) quantitative proteomics method to identify and quantify the protein composition of two generations EVs from three different donors and analysed the function and possible mechanism of action of the proteins in EVs of hUC-MSCs via bioinformatics. By comparative proteomic analysis, we characterized the different passages EVs. Furthermore, we found that adaptor-related protein complex 2 subunit alpha 1 (AP2A1) and adaptor-related protein complex 2 subunit beta 1 (AP2B1) in hUC-MSC-derived EVs may play a significant role in the treatment of Alzheimer's disease (AD) by regulating the synaptic vesicle cycle signalling pathway. Our work provides a direction for batch-to-batch quality control of hUC-MSC-derived EVs and their application in AD treatment.
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Enfermedad de Alzheimer , Vesículas Extracelulares , Células Madre Mesenquimatosas , Humanos , Enfermedad de Alzheimer/metabolismo , Proteómica , Complejo 2 de Proteína Adaptadora/metabolismo , Vesículas Extracelulares/metabolismoRESUMEN
Konjac glucomannan (KGM) hydrolysate exhibit various biological activities and health-promoting effects. Lytic polysaccharide monooxygenases (LPMOs) play an important role on enzymatic degradation of recalcitrant polysaccharides to obtain fermentable sugars. It is generally accepted that LPMOs exhibits high substrate specificity and oxidation regioselectivity. Here, a bacteria-derived SmAA10A, with chitin-active with strict C1 oxidation, was used to catalyse KGM degradation. Through ethanol precipitation, two hydrolysed KGM components (4â¯kDa (KGM-1) and 5â¯kDa (KGM-2)) were obtained that exhibited antibacterial activity against Staphylococcus aureus. In natural KGM, KGM-1, and KGM-2, the molar ratios of mannose to glucose were 1:2.19, 1:3.05, and 1:2.87, respectively, indicating that SmAA10A preferentially degrades mannose in KGM. Fourier-transform infrared spectroscopy and scanning electron microscopy imaging revealed the breakage of glycosylic bonds during enzymatic catalysis. The regioselectivity of SmAA10A for KGM degradation was determined based on the fragmentation behaviour of the KGM-1 and KGM-2 oligosaccharides and their NaBD4-reduced forms. SmAA10A exhibited diverse oxidation degradation of KGM and generated single C1-, single C4-, and C1/C4-double oxidised oligosaccharide forms. This study provides an alternative method for obtaining KGM degradation components with antibacterial functions and expands the substrate specificity and oxidation regioselectivity of bacterial LPMOs.
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Antibacterianos , Mananos , Oxigenasas de Función Mixta , Oxidación-Reducción , Mananos/química , Mananos/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/metabolismo , Oxigenasas de Función Mixta/metabolismo , Oxigenasas de Función Mixta/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/enzimología , Especificidad por Sustrato , HidrólisisRESUMEN
A20-binding inhibitor of NF-κB activation (ABIN1) is a polyubiquitin-binding protein that regulates cell death and immune responses. Although Abin1 is located on chromosome 5q in the region commonly deleted in patients with 5q minus syndrome, the most distinct of the myelodysplastic syndromes (MDSs), the precise role of ABIN1 in MDSs remains unknown. In this study, mice with a mutation disrupting the polyubiquitin-binding site (Abin1Q478H/Q478H ) is generated. These mice develop MDS-like diseases characterized by anemia, thrombocytopenia, and megakaryocyte dysplasia. Extramedullary hematopoiesis and bone marrow failure are also observed in Abin1Q478H/Q478H mice. Although Abin1Q478H/Q478H cells are sensitive to RIPK1 kinase-RIPK3-MLKL-dependent necroptosis, only anemia and splenomegaly are alleviated by RIPK3 deficiency but not by MLKL deficiency or the RIPK1 kinase-dead mutation. This indicates that the necroptosis-independent function of RIPK3 is critical for anemia development in Abin1Q478H/Q478H mice. Notably, Abin1Q478H/Q478H mice exhibit higher levels of type I interferon (IFN-I) expression in bone marrow cells compared towild-type mice. Consistently, blocking type I IFN signaling through the co-deletion of Ifnar1 greatly ameliorated anemia, thrombocytopenia, and splenomegaly in Abin1Q478H/Q478H mice. Together, these results demonstrates that ABIN1(Q478) prevents the development of hematopoietic deficiencies by regulating type I IFN expression.
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Anemia , Interferón Tipo I , Trombocitopenia , Animales , Humanos , Ratones , Poliubiquitina , EsplenomegaliaRESUMEN
Fourier transform infrared (FTIR) microspectroscopy was applied to in-situ analyse the chemical change of tibial articular subchondral bone of female Hartley guinea pigs with age increase. Three infrared absorption regions (a, b, c) of trabecular bone and central marrow region of the subchondral bone were measured for guinea pigs of different ages (1 months, 2 months and 3 months) using the infrared spectrum. Results show that (1) with months increasing, the total area of trabecular bone is increasing, meanwhile, the region a which is similar to normal trabecular bone spectra is decreasing, and region d waveform has the same trend as region a. (2) In the second and third month, region b & c show amide Ill redshift and the red shift in region c shows a shoulder peak, showing the absorption peak intensity on behalf of nucleic acid and polysaccharide in region b & c is 7 times that in region a. (3) beta glycosidic bond absorption peak appears at region c in 3 different old pigs. (4) I(amide III) / I(amide II) is the highest in region b in the second month but lowest in the third month; I(amide III) / I(amide II) reduces from a to c in the second and third month; I(upsilon3)PO2- / I(amide II) in region b & c is 7 times higher than region a in the second and third Month These results are consistent with the regular pattern of change rule of osteoarthritis subchondral bone's organization structure and chemical composition in different stages. Our primary result illustrated that FTIR microspectroscopy can be used for in-situ analysis of the molecular organization of subchondral trabecular bone and bone marrow. It provides reliable pathology information for osteoarthritis subchondral bone tissue at molecular level.
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Envejecimiento , Cartílago Articular , Espectroscopía Infrarroja por Transformada de Fourier , Tibia/anatomía & histología , Animales , Femenino , Cobayas , OsteoartritisRESUMEN
Background and Purpose: Radiomics features and The Visually AcceSAble Rembrandt Images (VASARI) standard appear to be quantitative and qualitative evaluations utilized to determine glioma grade. This study developed a preoperative model to predict glioma grade and improve the efficacy of clinical strategies by combining these two assessment methods. Materials and Methods: Patients diagnosed with glioma between March 2017 and September 2018 who underwent surgery and histopathology were enrolled in this study. A total of 3840 radiomic features were calculated; however, using the least absolute shrinkage and selection operator (LASSO) method, only 16 features were chosen to generate a radiomic signature. Three predictive models were developed using radiomic features and VASARI standard. The performance and validity of models were evaluated using decision curve analysis and 10-fold nested cross-validation. Results: Our study included 102 patients: 35 with low-grade glioma (LGG) and 67 with high-grade glioma (HGG). Model 1 utilized both radiomics and the VASARI standard, which included radiomic signatures, proportion of edema, and deep white matter invasion. Models 2 and 3 were constructed with radiomics or VASARI, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.937 and 0.831, respectively, which was less than that of Model 1, with an AUC of 0.966. Conclusion: The combination of radiomics features and the VASARI standard is a robust model for predicting glioma grades.
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Aim: This study investigated the effect of allografting umbilical cord blood mononuclear cells (UCBMCs) into the scrotum on sexual function in male elderly mice. Methods: UCBMCs were injected once into the scrotal sheath cavity of elderly mice. Results: The transplanted UCBMCs survived in the scrotal sheath cavity for 1 month. The mice had significantly increased blood testosterone concentrations, cyclic guanosine monophosphate (cGMP) levels and total nitric oxide synthase (T-NOS) activity in the corpus cavernosum and an increase in the number of mouse matings within 30 min (all p = 0.000). Conclusion: Scrotum-implanted UCBMCs improve the sexual function of male elderly mice through testosterone production and the NOS/cGMP pathway, which may provide an innovative transplantation approach for the treatment of erectile dysfunction.
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Disfunción Eréctil , Sangre Fetal , Humanos , Ratones , Masculino , Animales , Anciano , Sangre Fetal/metabolismo , Escroto/metabolismo , Disfunción Eréctil/metabolismo , Pene/metabolismo , GMP Cíclico/metabolismo , GMP Cíclico/farmacología , Testosterona/metabolismo , Testosterona/farmacologíaRESUMEN
In the present study, we reported the allele frequencies for new 21 autosomal short tandem repeat (STR) loci, including D6S474, D12ATA63, D22S1045, D10S1248, D1S1677, D11S4463, D1S1627, D3S4529, D2S441, D6S1017, D4S2408, D19S433, D17S1301, D1GATA113, D18S853, D20S482, D14S1434, D9S1122, D2S1776, D10S1435 and D5S2500 loci. Forensic statistical parameters were estimated from a sample set of 120 unrelated healthy individuals from the Salar ethnic group in Xunhua Salar Autonomous County of Qinghai province, China. A total of 151 alleles were observed at 21 STR loci in the population, and their allele frequencies were in the range of 0.004-0.554. All STR loci showed a high degree of genetic polymorphisms, and the combined probability of exclusion, combined power of discrimination and combined probability of matching for all 21 STR loci were 0.9999993134, 0.99999999999999999991739 and 8.2607 × 10(-20), respectively. For all the 21 STR loci in the Salar ethnic group, the observed genotypic data showed no significant deviation from those expected under the Hardy-Weinberg equilibrium. The allele frequency distributions for the 21 autosomal STR loci were compared between the Salar group and its neighboring populations and significant differences were detected among these populations at D1S1677, D2S441, D3S4529, D4S2408, D6S1017, D11S4463, D12ATA63, D14S14343, D18S853, D19S433 and D22S1045 loci.
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Etnicidad/genética , Variación Genética , Repeticiones de Microsatélite/genética , Análisis de Varianza , China , Electroforesis Capilar , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento/genética , Reacción en Cadena de la PolimerasaRESUMEN
Chitinolytic ß-N-acetyl-d-hexosaminidases, as a class of chitin hydrolysis enzyme in insects, are a potential species-specific target for developing environmentally-friendly pesticides. Until now, pesticides targeting chitinolytic ß-N-acetyl-d-hexosaminidase have not been developed. This study demonstrates a combination of different theoretical methods for investigating the key structural features of this enzyme responsible for pesticide inhibition, thus allowing for the discovery of novel small molecule inhibitors. Firstly, based on the currently reported crystal structure of this protein (OfHex1.pdb), we conducted a pre-screening of a drug-like compound database with 8 × 10(6) compounds by using the expanded pesticide-likeness criteria, followed by docking-based screening, obtaining 5 top-ranked compounds with favorable docking conformation into OfHex1. Secondly, molecular docking and molecular dynamics simulations are performed for the five complexes and demonstrate that one main hydrophobic pocket formed by residues Trp424, Trp448 and Trp524, which is significant for stabilization of the ligand-receptor complex, and key residues Asp477 and Trp490, are respectively responsible for forming hydrogen-bonding and π-π stacking interactions with the ligands. Finally, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis indicates that van der Waals interactions are the main driving force for the inhibitor binding that agrees with the fact that the binding pocket of OfHex1 is mainly composed of hydrophobic residues. These results suggest that screening the ZINC database can maximize the identification of potential OfHex1 inhibitors and the computational protocol will be valuable for screening potential inhibitors of the binding mode, which is useful for the future rational design of novel, potent OfHex1-specific pesticides.
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Quitina/metabolismo , Quitinasas/farmacología , Insectos/enzimología , Plaguicidas/farmacología , beta-N-Acetilhexosaminidasas/antagonistas & inhibidores , Animales , Sitios de Unión , Quitinasas/síntesis química , Quitinasas/química , Descubrimiento de Drogas , Hidrólisis , Interacciones Hidrofóbicas e Hidrofílicas , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Plaguicidas/síntesis química , Plaguicidas/química , Distribución de Poisson , Conformación ProteicaRESUMEN
In-situ analysis the chemical composition of tibial articular cartilage of female Hartley guinea pigs with Fourier transform infrared (FTIR) microspectroscopy was conducted. The infrared spectrum survey consists of three ages (1 months, 2 months and 3 months) and three cartilage layers (surface, middle and deep). The results demonstrated that with ages increasing, the peak positions of main absorbance bands in surface and middle shifted to a lower wavenumber, and in deep they shifted to a lower wavenumber first, then shifted to a higher wavenumber. Infrared spectrum character of collagen, nucleic acid and proteoglycan were compared and analyzed. The ratios of I1 657/I 1 548, I1 074/I1 548 and I1 074/I1 237 tend to decrease with ages increasing in surface and middle. However, the ratios at 2 months are less than other ages in deep. These results are consistent with the regular pattern of cartilage ingredient change in different degradation stage, while the tibial platform images created by microscopic spectral imaging technology is highly compliant with pathology description. The authors' primary result illustrated that FTIR microspectroscopy can be used for in-situ analysis of molecular constituents of different levels cartilages. The molecular information obtained from the study is important for understanding the pathogenesis of cartilage diseases.