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Histone chaperone FACT (facilitates chromatin transcription) is well known to promote chromatin recovery during transcription. However, the mechanism how FACT regulates genome-wide chromatin accessibility and transcription factor binding has not been fully elucidated. Through loss-of-function studies, we show here that FACT component Ssrp1 is required for DNA replication and DNA damage repair and is also essential for progression of cell phase transition and cell proliferation in mouse embryonic fibroblast cells. On the molecular level, absence of the Ssrp1 leads to increased chromatin accessibility, enhanced CTCF binding, and a remarkable change in dynamic range of gene expression. Our study thus unequivocally uncovers a unique mechanism by which FACT complex regulates transcription by coordinating genome-wide chromatin accessibility and CTCF binding.
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Factor de Unión a CCCTC , Cromatina , Proteínas de Unión al ADN , Regulación de la Expresión Génica , Proteínas del Grupo de Alta Movilidad , Chaperonas de Histonas , Animales , Ratones , Factor de Unión a CCCTC/genética , Factor de Unión a CCCTC/metabolismo , Cromatina/genética , Replicación del ADN , Chaperonas de Histonas/genética , Proteínas de Unión al ADN/genética , Proteínas del Grupo de Alta Movilidad/genética , Células 3T3 NIH , Reparación del ADNRESUMEN
In this paper, an intelligent blind guide system based on 2D LiDAR and RGB-D camera sensing is proposed, and the system is mounted on a smart cane. The intelligent guide system relies on 2D LiDAR, an RGB-D camera, IMU, GPS, Jetson nano B01, STM32, and other hardware. The main advantage of the intelligent guide system proposed by us is that the distance between the smart cane and obstacles can be measured by 2D LiDAR based on the cartographer algorithm, thus achieving simultaneous localization and mapping (SLAM). At the same time, through the improved YOLOv5 algorithm, pedestrians, vehicles, pedestrian crosswalks, traffic lights, warning posts, stone piers, tactile paving, and other objects in front of the visually impaired can be quickly and effectively identified. Laser SLAM and improved YOLOv5 obstacle identification tests were carried out inside a teaching building on the campus of Hainan Normal University and on a pedestrian crossing on Longkun South Road in Haikou City, Hainan Province. The results show that the intelligent guide system developed by us can drive the omnidirectional wheels at the bottom of the smart cane and provide the smart cane with a self-leading blind guide function, like a "guide dog", which can effectively guide the visually impaired to avoid obstacles and reach their predetermined destination, and can quickly and effectively identify the obstacles on the way out. The mapping and positioning accuracy of the system's laser SLAM is 1 m ± 7 cm, and the laser SLAM speed of this system is 25~31 FPS, which can realize the short-distance obstacle avoidance and navigation function both in indoor and outdoor environments. The improved YOLOv5 helps to identify 86 types of objects. The recognition rates for pedestrian crosswalks and for vehicles are 84.6% and 71.8%, respectively; the overall recognition rate for 86 types of objects is 61.2%, and the obstacle recognition rate of the intelligent guide system is 25-26 FPS.
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GRT-X, which targets both the mitochondrial translocator protein (TSPO) and the Kv7.2/3 (KCNQ2/3) potassium channels, has been shown to efficiently promote recovery from cervical spine injury. In the present work, we investigate the role of GRT-X and its two targets in the axonal growth of dorsal root ganglion (DRG) neurons. Neurite outgrowth was quantified in DRG explant cultures prepared from wild-type C57BL6/J and TSPO-KO mice. TSPO was pharmacologically targeted with the agonist XBD173 and the Kv7 channels with the activator ICA-27243 and the inhibitor XE991. GRT-X efficiently stimulated DRG axonal growth at 4 and 8 days after its single administration. XBD173 also promoted axonal elongation, but only after 8 days and its repeated administration. In contrast, both ICA27243 and XE991 tended to decrease axonal elongation. In dissociated DRG neuron/Schwann cell co-cultures, GRT-X upregulated the expression of genes associated with axonal growth and myelination. In the TSPO-KO DRG cultures, the stimulatory effect of GRT-X on axonal growth was completely lost. However, GRT-X and XBD173 activated neuronal and Schwann cell gene expression after TSPO knockout, indicating the presence of additional targets warranting further investigation. These findings uncover a key role of the dual mode of action of GRT-X in the axonal elongation of DRG neurons.
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Axones , Ganglios Espinales , Receptores de GABA , Animales , Ganglios Espinales/metabolismo , Ganglios Espinales/citología , Ratones , Axones/metabolismo , Receptores de GABA/metabolismo , Receptores de GABA/genética , Canal de Potasio KCNQ2/metabolismo , Canal de Potasio KCNQ2/genética , Ratones Noqueados , Ratones Endogámicos C57BL , Células Cultivadas , Células de Schwann/metabolismo , Células de Schwann/efectos de los fármacos , Células de Schwann/citología , Técnicas de Cocultivo , Neuronas/metabolismo , Neuronas/efectos de los fármacosRESUMEN
Cerebral infarction is one of the most prevalent cerebrovascular disorders. Microglia and infiltrating macrophages play a key role in regulating the inflammatory response after ischemic stroke. Regulation of microglia/macrophages polarization contributes to the recovery of neurological function in cerebral infarction. In recent decades, human umbilical cord blood mononuclear cells (hUCBMNCs) have been considered a potential therapeutic alternative. However, the mechanism of action is yet unclear. Our study aimed to explore whether hUCBMNCs treatment for cerebral infarction is via regulation of microglia/macrophages polarization. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and were treated by intravenous routine with or without hUCBMNCs at 24 h following MCAO. We evaluated the therapeutic effects of hUCBMNCs on cerebral infarction by measuring animal behavior and infarct volume, and further explored the possible mechanisms of hUCBMNCs for cerebral infarction by measuring inflammatory factors and microglia/macrophages markers using Elisa and immunofluorescence staining, respectively. We found that administration with hUCBMNCs improved behavioral functions and reduced infarct volume. Rats treated with hUCBMNCs showed a significant reduction in the level of IL-6, and TNF-α and increased the level of IL-4 and IL-10 compared to those treated without hUCBMNCs. Furthermore, hUCBMNCs inhibited M1 polarization and promoted M2 polarization of microglia/macrophages after MCAO. We conclude that hUCBMNCs could ameliorate cerebral brain injury by promoting microglia/macrophages M2 polarization in MCAO Rats. This experiment provides evidence that hUCBMNCs represent a promising therapeutic option for ischemic stroke.
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Lesiones Encefálicas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratas , Humanos , Masculino , Animales , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Microglía , Sangre Fetal , Ratas Sprague-Dawley , Isquemia Encefálica/tratamiento farmacológico , MacrófagosRESUMEN
Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.
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Edema Encefálico , Paro Cardíaco , Hipotermia Inducida , Hipoxia Encefálica , Animales , Encéfalo , Edema Encefálico/etiología , Paro Cardíaco/complicaciones , Paro Cardíaco/terapia , Humanos , Hipoxia Encefálica/complicaciones , RatonesRESUMEN
Laser sensing and vision sensing smart canes can improve the convenience of travel for the visually impaired, but for the present, most of the system functions of laser sensing and vision sensing smart canes are still defective. Guide equipment and smart blind canes are introduced and classified first, and the smart blind canes based on vision sensing, laser sensing and laser vision sensing are investigated, respectively, and the research status of laser vision sensing smart blind canes is sorted out. The advantages and disadvantages of various laser vision sensing smart blind canes are summarized, especially the research development of laser vision fusion as the core of new smart canes. The future development prospects of laser vision sensing smart blind cane are overviewed, to boost the development of laser vision sensing smart blind cane, to provide safe and efficient travel guarantee for the visually impaired.
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Bastones , Personas con Daño Visual , Humanos , Diseño de Equipo , CegueraRESUMEN
The 18 kDa translocator protein (TSPO/PBR) is a multifunctional evolutionary highly conserved outer mitochondrial membrane protein. Decades of research has reported an obligatory role of TSPO/PBR in both mitochondrial cholesterol transport and, thus, steroid production. However, the strict dependency of steroidogenesis on TSPO/PBR has remained controversial. The aim of this study was to provide insight into the steroid profile in complete C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout male mice (TSPO-KO) under basal conditions. The steroidome in the brain, adrenal glands, testes and plasma was measured by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). We found that steroids present in wild-type (WT) mice were also detected in TSPO-KO mice, including pregnenolone (PREG), progestogens, mineralo-glucocorticosteroids and androgens. The concentrations of PREG and most metabolites were similar between genotypes, except a significant decrease in the levels of the 5α-reduced metabolites of progesterone (PROG) in adrenal glands and plasma and of the 5α-reduced metabolites of corticosterone (B) in plasma in TSPO-KO compared to WT animals, suggesting other regulatory functions for the TSPO/PBR. The expression levels of the voltage-dependent anion-selective channel (VDAC-1), CYP11A1 and 5α-reductase were not significantly different between both groups. Thus, the complete deletion of the tspo gene in male mice does not impair de novo steroidogenesis in vivo.
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Receptores de GABA , Espectrometría de Masas en Tándem , Masculino , Ratones , Animales , Receptores de GABA/genética , Receptores de GABA/metabolismo , Ratones Noqueados , Ratones Endogámicos C57BL , Esteroides , Proteínas Portadoras , PregnenolonaRESUMEN
Objective: To analyze the application effect of continuous lumbar cistern fluid drainage combined with decompressive craniectomy in the treatment of severe craniocerebral injury. Methods: A total of 87 patients with severe craniocerebral injury admitted to our hospital between March 2016 and March 2021 were retrospectively enrolled. They were divided into two groups according to the decompression methods applied, with 42 patients who received standard decompressive craniectomy assigned to the control group and 45 patients who received continuous lumbar cistern fluid drainage combined with standard decompressive craniectomy assigned to the observation group. The primary indicators that were monitored and compared between the two group included the amount of time for patient CT imaging to be clear of subarachnoid hemorrhage, the length-of-stay, the duration of post-operative intubation, the mannitol dose, scores for Glasgow Coma Scale (GCS), prognosis, the incidence of cerebral edema and cerebral infarction, and complications. The secondary indicators that were monitored and compared included intracranial pressure, cerebrospinal fluid antinucleosome protein SP100, and red blood cell count of the two groups before treatment and after continuous drainage for 7 days. Results: The amount of time for CT imaging to be clear of subarachnoid hemorrhage and the length-of-stay of the observation group were shorter than those of the control group, the mannitol dose of the observation group was lower than that of the control group, the incidence of cerebral edema and the incidence of complications of the observation group were lower than those of the control group, and the rate of patients with good prognosis in the observation group was higher than that in the control group ( P<0.05). There was no significant difference in the rate of poor prognosis or mortality between the two groups ( P>0.05). The duration of postoperative intubation of the observation group was (8.24±1.09) d, while that of the control group was (9.22±1.26) d, and the difference between the two groups was statistically significant ( t=3.887, P<0.05). There were 2 cases (4.44%) of cerebral infarction in the observation group, with the infarct volume being (8.36±1.87) cm 3, while there were 9 cases (21.43%) of cerebral infarction in the control group, with the infarct volume being (8.36±1.87) cm 3, and there were statistically significant differences in the incidence and volume of cerebral infarction between the two groups ( χ 2=5.674, t=9.609, P<0.05). After treatment, the intracranial pressure and red blood cell count decreased in both groups and the intracranial pressure, cerebrospinal fluid SP100, and red blood cell count of the observation group were significantly lower than those of the control group ( P<0.05). The cerebrospinal fluid SP100 of the observation group decreased after treatment in comparison with the level before treatment ( P<0.05), while the pre- and post-treatment levels of the control group did not demonstrate any significant difference. Conclusion: Continuous lumbar cistern fluid drainage in patients with severe craniocerebral injury effectively shortens the time required for the body to recover, significantly reduces the level of intracranial pressure, improves the levels of cerebral edema and cerebral infarction, and has a high degree of safety for prognosis and recovery.
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Edema Encefálico , Traumatismos Craneocerebrales , Craniectomía Descompresiva , Hemorragia Subaracnoidea , Humanos , Craniectomía Descompresiva/métodos , Edema Encefálico/etiología , Hemorragia Subaracnoidea/cirugía , Hemorragia Subaracnoidea/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Traumatismos Craneocerebrales/tratamiento farmacológico , Traumatismos Craneocerebrales/cirugía , Drenaje/métodos , Manitol/uso terapéutico , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/cirugíaRESUMEN
BACKGROUND: In an investigation of hospital-acquired mucormycosis cases among transplant recipients, healthcare linens (HCLs) delivered to our center were found to be contaminated with Mucorales. We describe an investigation and remediation of Mucorales contamination at the laundry supplying our center. METHODS: We performed monthly RODAC cultures of HCLs upon hospital arrival, and conducted site inspections and surveillance cultures at the laundry facility. Remediation was designed and implemented by infection prevention and facility leadership teams. RESULTS: Prior to remediation, 20% of HCLs were culture-positive for Mucorales upon hospital arrival. Laundry facility layout and processes were consistent with industry standards. Significant step-ups in Mucorales and mold culture-positivity of HCLs were detected at the post-dryer step (0% to 12% [P = .04] and 5% to 29% [P = .01], respectively). Further increases to 17% and 40% culture-positivity, respectively, were noted during pre-transport holding. Site inspection revealed heavy Mucorales-positive lint accumulation in rooftop air intake and exhaust vents that cooled driers; intake and exhaust vents that were facing each other; rooftop and plant-wide lint accumulation, including in the pre-transport clean room; uncovered carts with freshly-laundered HCLs. Following environmental remediation, quality assurance measures and education directed toward these sources, Mucorales culture-positivity of newly-delivered HCLs was reduced to 0.3% (P = .0001); area of lint-contaminated rooftop decreased from 918 m2 to 0 m2 on satellite images. CONCLUSIONS: Targeted laundry facility interventions guided by site inspections and step-wise culturing significantly reduced Mucorales-contaminated HCLs delivered to our hospital. Collaboration between infection prevention and laundry facility teams was crucial to successful remediation.
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Mucorales , Mucormicosis , Ropa de Cama y Ropa Blanca , Atención a la Salud , Hospitales , Humanos , Mucormicosis/diagnóstico , Mucormicosis/epidemiologíaRESUMEN
Accumulations of ice on modern infrastructures often cause severe consequences. As such, there is significant interest in developing functional coatings/surfaces that can prevent this. One such approach has been demonstrated with slippery liquid-infused porous surfaces (SLIPS) and organogels where the ice adhesion strength is reduced to the critical point (less than 10 kPa) where it can be removed by natural forces such as gravity, wind, vibrations, and so forth. However, both designs are limited by lubricant depletion. If lubricant release and reabsorption (syneresis) of organogels can be arbitrarily controlled by the surrounding temperature, the loss due to unfavorable evaporation and drainage of infused lubricants can be minimized and its durability can be extended. This study demonstrates the tunable thermo-responsive syneresis of transparent fluorinated organogels (F-ORGs) prepared from a commercial silicone elastomer and a lubricant mixture of fluorinated silicone oil and either poly(dimethylsiloxane) or poly(methylphenylsiloxane). By carefully tuning the ratio of the two lubricants in the mixture, the corresponding F-ORGs demonstrated arbitrarily tunable critical syneresis temperatures from -15 to 40 °C, below which the lubricant is released on the surface and above which the lubricant is re-absorbed. The resulting surfaces showed not only exceptionally long-lasting/repeatable low ice adhesion strengths (≤10 kPa over 50 icing/de-icing cycles) but also significant improvements in their repellency toward a variety of organic liquids. Compared to non-fluorinated organogels, F-ORGs could offer improved protection against outdoor pollutants to further enhance their practicality.
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To develop a current plant lighting source with both a suitable illumination area and high illumination uniformity, we propose a lighting system for plant growth based on the combination of laser diode and LED lighting modes. We added a triangular-prism-shaped base plate element to the previous array type optical structure to increase the light coupling degree and expand the illumination area. The Taguchi method was used in our design and experiment, and the influence of different factors on the illumination uniformity was studied and compared to the lighting effect of a traditional array floor structure. Finally, a plant lighting source with an illumination uniformity of 88.54% and color-mixing uniformity of 84.75% was obtained. Compared to the commonly adopted array structure, this plant lighting source expands the illumination area by 31.03%, which verifies the effectiveness of the scheme.
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Iluminación , Iluminación/métodosRESUMEN
The synthetic jet piezoelectric air pump is a potential miniature device for electronic cooling. In order to improve the performance of the device, a small-sized synthetic jet piezoelectric air pump is proposed in this work, which is mainly characterized by petal-shaped inlet channels. First, the structure and working principle of the piezoelectric vibrator and the proposed pump are analyzed. Then, three synthetic jet piezoelectric air pumps with different inlet channels are compared. These inlets are the direct channels, the diffuser/nozzle channels, and the petal-shaped channels, respectively. Furthermore, the performance of the synthetic jet piezoelectric air pump with the petal-shaped inlet channels is optimized by orthogonal tests. Finally, the simulation was used to investigate the heat dissipation capability of the synthetic jet piezoelectric pump. The experimental results show that among the three inlet channels, the petal-shaped channel can greatly improve the performance of the pump. The unoptimized pump with petal-shaped channels has a maximum flow rate of 1.8929 L/min at 100 V, 3.9 kHz. Additionally, the optimized pump with petal-shaped channels reaches a maximum flow rate of 3.0088 L/min at 100 V, 3.7 kHz, which is 58.95% higher than the unoptimized one. The proposed synthetic jet piezoelectric air pump greatly improves the output performance and has the advantages of simple structure, low cost, and easy integration. The convective heat transfer coefficient of the synthetic jet piezoelectric pump is 28.8 W/(m2·°C), which can prove that the device has a better heat dissipation capability.
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In this paper, a pressure sensor based on a metal diaphragm and lever structure is designed, the sensing principle and mechanical structure of this sensor are analyzed and simulated, and its sensitization effectiveness and temperature compensation are verified. The maximum deflections of metal diaphragms of different sizes and materials were compared, and it was found that the square beryllium bronze diaphragm with a thickness of 1 mm and a side length of 20 mm had good elastic properties. The influence of the FBG in different positions of the lever on the center wavelength is analyzed. The sensitivity of the bare FBG is markedly improved under the influence of the two structures of the square elastic diaphragm and the lever, with a typical pressure sensitivity of 3.35 nm/MPa at 3 mm to the left of the lever center. The purpose of temperature compensation is achieved by adding another FBG that measures the temperature, and the sensing sensitivity can be tuned by adjusting the position of the FBG. It can meet the detection needs of a small range and high sensitivity.
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The electrical sensing elements used in the traditional XBT (Expendable Bathythermograph) have problems such as low sensitivity and slow response time, and it is difficult to overcome the complex marine environment using the time-depth formula. In this paper, an ocean temperature depth sensor based on brass diaphragm and liquid filling is designed. The stress response time of FBGs with different lengths and the heat transfer time of different liquid materials are compared, and it is found that a fast response of 51 ms can be obtained by using GaInSn liquid for temperature sensing. The center deflection changes of brass diaphragms with different radii are analyzed, and the brass diaphragms with radius and thickness of 10 mm and 1 mm are selected, which still have good elastic properties under the pressure of 5 MPa. The influence of the inner metal shell section radius on the temperature and depth sensitivity is analyzed. When the final section radius is 3 mm, the temperature sensitivity of the sensor is 1.065 nm/°C, the pressure sensitivity is 1.245 nm/MPa, and the response time of temperature and depth is relatively close. Compared with the traditional temperature and depth sensors using empirical formulas for calculation, the data accuracy is improved, and a wide range of sensitivity can be tuned by adjusting the size of the internal metal shell, which can meet the needs of ocean temperature and depth data detection with high sensitivity and fast response time.
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BACKGROUND: Immunotherapies including PD-1/PD-L1 antibodies have been approved for the treatment of Muscle-invasive Bladder Cancer (MIBC) patients. However, immunotherapies could only be beneficial for about 20% MIBC patients. Thus, identification of the immune subtype is becoming increasingly important. This study aimed to explore the immune subtype by analyzing the gene expression profiles. METHODS: A total of 6 datasets including (GSE13507, GSE31684, GSE32548, GSE32894, GSE69795, and TCGA-BLCA) were downloaded. The gene expression profiles from different datasets were combined since the batch effects were removed. We performed unsupervised clustering analysis to identify the immune subtype by the combined gene expression profiles. The tumor-infiltration levels of 22 immune cells, immune scores, and tumor purity were calculated, and the survival analysis was performed to investigate the prognosis difference between immune subtypes. The enriched pathways for each immune subtype were obtained. RESULTS: We identified four novel immune subtypes (referred to S1, S2, S3, and S4) among MIBC patients. We found that S1 was enriched in immune scores had the best prognosis. In contrast, S3 was poor in immune scores and had the worst prognosis. Subtype S1, S2, S3, and S4 were enriched in immune-related pathways, extracellular matrix-related pathways, metabolism-related pathways, and cancer-related pathways, respectively. CONCLUSION: The current study suggests that the immune subtypes based on gene expression profiles could contribute to select the appropriate MIBC patient for immunotherapies.
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Neoplasias de la Vejiga Urinaria , Análisis por Conglomerados , Humanos , Músculos/patología , Pronóstico , Transcriptoma , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
BACKGROUND: The number of myofiber is determined during the embryonic stage and does not increase during the postnatal period for birds, including goose. Thus, muscle production of adult goose is pre-determined during embryogenesis. Previous studies show N6-methyladenosine (m6A) is an important regulator for skeletal muscle development of birds and miRNAs play as a co-regulator for the skeletal muscle development in birds. Herein, we sequenced m6A and miRNA transcriptomes to investigate the profiles of m6A and their potential mechanism of regulating breast muscle development in Dingan Goose. RESULTS: We selected embryonic 21th day (E21) and embryonic 30th day (E30) to investigate the roles of transcriptome-wide m6A modification combining with mRNAs and miRNAs in goose breast muscle development. In this study, m6A peaks were mainly enriched in coding sequence (CDS) and start codon and397 genes were identified as differentially methylated genes (DMGs). GO and KEGG analysis showed that DMGs were highly related to cellular and metabolic process and that most DMGs were enriched in muscle-related pathways including Wnt signaling pathway, mTOR signaling and FoxO signaling pathway. Interestingly, a negative correlation between m6A methylation level and mRNA abundance was found through the analysis of m6A-RNA and RNA-seq data. Besides, we found 26 muscle-related genes in 397 DMGs. We also detected 228 differentially expressed miRNAs (DEMs), and further found 329 genes shared by the target genes of DEMs and DMGs (m6A-miRNA-genes), suggesting a tightly relationship between DEMs and DMGs. Among the m6A-miRNA-genes, we found 10 genes are related to breast muscle development. We further picked out an m6A-miRNA-gene, PDK3, from the 10 genes to visualize it and the result showed differentially methylated peaks on the mRNA transcript consistent with our m6A-seq results. CONCLUSION: GO and KEGG of DMGs between E21 and E30 showed most DMGs were muscle-related. In total, 228 DEMs were found, and the majority of DMGs were overlapped with the targets of DEGs. The differentially methylated peaks along with an m6A-miRNA-gene, PDK3, showed the similar results with m6A-seq results. Taken together, the results presented here provide a reference for further investigation of embryonic skeletal muscle development mechanism in goose.
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Gansos , Transcriptoma , Animales , Desarrollo Embrionario , Gansos/genética , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Desarrollo de Músculos/genéticaRESUMEN
Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA, RB1, FGFR3, KMT2C, MACF1, RYR2, and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.
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Biomarcadores de Tumor/genética , Linfocitos T CD8-positivos/citología , Neoplasias de la Vejiga Urinaria/clasificación , Humanos , Músculos/patología , Mutación , Fenotipo , Transducción de Señal , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
Chemically and spatially micropatterned surfaces have been successfully prepared for a number of diverse applications, including water/fog harvesting, screen printing, microfluidics, and cell/protein assays. While there have been quite some reports on micropatterned surfaces, less is known about the factors that influence dynamic surface wettability. To that end, smooth checkerboard-like micropatterned hydrophobic/(super)hydrophilic surfaces (2, 5, 10, 20 µm pattern sizes) with regions of matching/mismatching contact angle hysteresis (CAH) were prepared on the basis of a simple chemisorption/photopatterning of monolayers. The effects of regional wettability/CAH and pattern size on the overall dynamic wettability were then examined by measuring the dynamic contact angles (CAs) and substrate tilt angles (θT) of water. It was found that the dynamic wettability on samples with matching regional CAH remained unchanged, even when using hydrophilic regions or changing the pattern size. In contrast, surfaces containing mismatching CAH regions pinned water droplets, leading to overall dynamic wetting properties markedly dependent on pattern size. In addition, the experimental data did not match values predicted by the Cassie equation because dynamic wetting behavior is dominated not by interfacial area but by the interactions of the liquid and solid at the three-phase contact line.
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OBJECTIVE: Increased permeability and changes in gut microbiota contributed to the pathogenesis of Alzheimer's disease (AD). Zonulin is a key modulator that regulates intestinal barrier function. Peripheral platelet alterations have been involved in AD pathology. C-type lectin-like receptor 2 (CLEC-2) is a receptor on the platelet surface for activation. The purpose of this study was to determine zonulin and CLEC-2 levels in mild cognitive impairment (MCI) and AD, and investigate the relationship between zonulin and CLEC-2. METHODS: In this study, CLEC-2 and zonulin levels were measured using ELISA assay in 110 AD patients, 110 MCI patients, and 110 non-demented control subjects. RESULTS: Increased CLEC-2 and zonulin levels were observed in MCI and AD patients. Furthermore, AD patients had higher CLEC-2 and zonulin levels compared with MCI patients. In addition, CLEC-2 levels were positively correlated with zonulin levels, after adjusting confounding factors (r = .592, P < .001). Multivariate analysis revealed that increased CLEC-2 and zonulin levels were significantly associated with reduced Mini-Mental State Examination (MMSE) score. CONCLUSIONS: C-type lectin-like receptor 2 is correlated with zonulin after adjusting confounding covariates. Moreover, increased CLEC-2 and zonulin are the significant factors for reduced MMSE score in MCI and AD. Further studies are needed.
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Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico , Lectinas Tipo C/sangre , Precursores de Proteínas/sangre , Anciano , Enfermedad de Alzheimer/sangre , Biomarcadores/sangre , Disfunción Cognitiva/sangre , Femenino , Haptoglobinas , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The nucleosome is the fundamental structural unit of eukaryotic chromatin and plays an essential role in the epigenetic regulation of cellular processes, such as DNA replication, recombination, and transcription. Hence, it is important to identify nucleosome positions in the genome. Our previous model based on DNA deformation energy, in which a set of DNA physical descriptors was used, performed well in predicting nucleosome dyad positions and occupancy. In this study, we established a machine-learning model for predicting nucleosome occupancy in order to further verify the physical descriptors. Results showed that (1) our model outperformed several other sequence compositional information-based models, indicating a stronger dependence of nucleosome positioning on DNA physical properties; (2) nucleosome-enriched and -depleted regions have distinct features in terms of DNA physical descriptors like sequence-dependent flexibility and equilibrium structure parameters; (3) gene transcription start sites and termination sites can be well characterized with the distribution patterns of the physical descriptors, indicating the regulatory role of DNA physical properties in gene transcription. In addition, we developed a web server for the model, which is freely accessible at http://lin-group.cn/server/iNuc-force/.