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Symbiotic microorganisms that reside on the host skin serve as the primary defense against pathogens in vertebrates. Specifically, the skin microbiome of bats may play a crucial role in providing resistance against Pseudogymnoascus destructans (Pd), the pathogen causing white-nose syndrome. However, the epidermis symbiotic microbiome and its specific role in resisting Pd in highly resistant bats in Asia are still not well understood. In this study, we collected and characterized skin microbiota samples of 19 Myotis pilosus in China and explored the differences between Pd-positive and negative individuals. We identified inhibitory effects of these bacteria through cultivation methods. Our results revealed that the Simpson diversity index of the skin microbiota for positive individuals was significantly lower than that of negative individuals, and the relative abundance of Pseudomonas was significantly higher in positive bats. Regardless of whether individuals were positive or negative for Pd, the relative abundance of potentially antifungal genera in skin microbiota was high. Moreover, we successfully isolated 165 microbes from bat skin and 41 isolates from positive individuals able to inhibit Pd growth compared to only 12 isolates from negative individuals. A total of 10 genera of Pd-inhibiting bacteria were screened, among which the genera Algoriella, Glutamicibacter, and Psychrobacter were newly discovered as Pd-inhibiting genera. These Pd-inhibiting bacteria metabolized a variety of volatile compounds, including dimethyl trisulfide, dimethyl disulfide, propylene sulfide, 2-undecanone, and 2-nonanone, which were able to completely inhibit Pd growth at low concentrations.IMPORTANCERecently, white-nose syndrome has caused the deaths of millions of hibernating bats, even threatening some with regional extinction. Bats in China with high resistance to Pseudogymnoascus destructans can provide a powerful reference for studying the management of white-nose syndrome and understanding the bats against the pathogen's intrinsic mechanisms. This study sheds light on the crucial role of host symbiotic skin microorganisms in resistance to pathogenic fungi and highlights the potential for harnessing natural defense mechanisms for the prevention and treatment of white-nose syndrome. In addition, this may also provide promising candidates for the development of bioinsecticides and fungicides that offer new avenues for addressing fungal diseases in wildlife and agricultural environments.
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Ascomicetos , Bacterias , Quirópteros , Hibernación , Microbiota , Piel , Quirópteros/microbiología , Animales , Piel/microbiología , Ascomicetos/aislamiento & purificación , Ascomicetos/fisiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , China , SimbiosisRESUMEN
Long terminal repeat retroelements (LTR-REs) have profound effects on DNA methylation and gene regulation. Despite the vast abundance of LTR-REs in the genome of Moso bamboo (Phyllostachys edulis), an industrial crop in underdeveloped countries, their precise implication of the LTR-RE mobility in stress response and development remains unknown. We investigated the RNA and DNA products of LTR-REs in Moso bamboo under various developmental stages and stressful conditions. Surprisingly, our analyses identified thousands of active LTR-REs, particularly those located near genes involved in stress response and developmental regulation. These genes adjacent to active LTR-REs exhibited an increased expression under stress and are associated with reduced DNA methylation that is likely affected by the induced LTR-REs. Moreover, the analyses of simultaneous mapping of insertions and DNA methylation showed that the LTR-REs effectively alter the epigenetic status of the genomic regions where they inserted, and concomitantly their transcriptional competence which might impact the stress resilience and growth of the host. Our work unveils the unusually strong LTR-RE mobility in Moso bamboo and its close association with (epi)genetic changes, which supports the co-evolution of the parasitic DNAs and host genome in attaining stress tolerance and developmental robustness.
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BACKGROUND: Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. This study aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy. METHODS: This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers between March 2021 and July 2022. A total of 1,883 patients scheduled to undergo gastroscopy were randomized to groups receiving 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety. RESULTS: The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%; risk difference, -0.64%; 97.5% CI, -2.2 to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, -10.8%; 97.5% CI, -14.0% to -8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group. CONCLUSIONS: This trial established the noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile.
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Gastroscopía , Propofol , Humanos , Método Simple Ciego , Benzodiazepinas , Peso Corporal , Hipnóticos y SedantesRESUMEN
Although CRISPR-Cas12a [clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 12a] combining pre-amplification technology has the advantage of high sensitivity in biosensing, its generality and specificity are insufficient, which greatly restrains its application range. Here, we discovered a new targeting substrate for LbaCas12a (Lachnospiraceae bacterium Cas12a), namely double-stranded DNA (dsDNA) with a sticky-end region (PAM-SE+ dsDNA). We discovered that CRISPR-Cas12a had special enzymatic properties for this substrate DNA, including the ability to recognize and cleave it without needing a protospacer adjacent motif (PAM) sequence and a high sensitivity to single-base mismatches in that substrate. Further mechanism studies revealed that guide RNA (gRNA) formed a triple-stranded flap structure with the substrate dsDNA. We also discovered the property of low-temperature activation of CRISPR-Cas12a and, by coupling with the unique DNA hybridization kinetics at low temperature, we constructed a complete workflow for low-abundance point mutation detection in real samples, which was fast, convenient and free of single-stranded DNA (ssDNA) transformation. The detection limits were 0.005-0.01% for synthesized strands and 0.01-0.05% for plasmid genomic DNA, and the mutation abundances provided by our system for 28 clinical samples were in accordance with next-generation sequencing results. We believe that our work not only reveals novel information about the target recognition mechanism of the CRISPR-Cas12a system, but also greatly broadens its application scenarios.
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Proteínas Asociadas a CRISPR , Sistemas CRISPR-Cas , Proteínas Asociadas a CRISPR/metabolismo , Proteínas Bacterianas/metabolismo , ADN/química , ADN de Cadena Simple/genéticaRESUMEN
The functional networks of the human brain exhibit the structural characteristics of a scale-free topology, and these neural networks are exposed to the electromagnetic environment. In this paper, we consider the effects of magnetic induction on synchronous activity in biological neural networks, and the magnetic effect is evaluated by the four-stable discrete memristor. Based on Rulkov neurons, a scale-free neural network model is established. Using the initial value and the strength of magnetic induction as control variables, numerical simulations are carried out. The research reveals that the scale-free neural network exhibits multiple coexisting behaviors, including resting state, period-1 bursting synchronization, asynchrony, and chimera states, which are dependent on the different initial values of the multi-stable discrete memristor. In addition, we observe that the strength of magnetic induction can either enhance or weaken the synchronization in the scale-free neural network when the parameters of Rulkov neurons in the network vary. This investigation is of significant importance in understanding the adaptability of organisms to their environment.
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BACKGROUND: Lysine glutarylation (Kglu) is one of the most important Post-translational modifications (PTMs), which plays significant roles in various cellular functions, including metabolism, mitochondrial processes, and translation. Therefore, accurate identification of the Kglu site is important for elucidating protein molecular function. Due to the time-consuming and expensive limitations of traditional biological experiments, computational-based Kglu site prediction research is gaining more and more attention. RESULTS: In this paper, we proposed GBDT_KgluSite, a novel Kglu site prediction model based on GBDT and appropriate feature combinations, which achieved satisfactory performance. Specifically, seven features including sequence-based features, physicochemical property-based features, structural-based features, and evolutionary-derived features were used to characterize proteins. NearMiss-3 and Elastic Net were applied to address data imbalance and feature redundancy issues, respectively. The experimental results show that GBDT_KgluSite has good robustness and generalization ability, with accuracy and AUC values of 93.73%, and 98.14% on five-fold cross-validation as well as 90.11%, and 96.75% on the independent test dataset, respectively. CONCLUSION: GBDT_KgluSite is an effective computational method for identifying Kglu sites in protein sequences. It has good stability and generalization ability and could be useful for the identification of new Kglu sites in the future. The relevant code and dataset are available at https://github.com/flyinsky6/GBDT_KgluSite .
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Lisina , Proteínas , Lisina/metabolismo , Proteínas/metabolismo , Secuencia de Aminoácidos , Procesamiento Proteico-Postraduccional , Mitocondrias/metabolismo , Biología Computacional/métodosRESUMEN
BACKGROUND: The study aims were to analyze pregnancy outcomes after the use of emergency cerclage in patients with different BMIs. METHODS: A total of 76 singleton pregnant patients who underwent emergency cerclage at a tertiary comprehensive hospital in China between Jan 2017 and Dec 2021 were retrospectively divided into an obesity group of 37 patients with BMIs ≥ 28 kg/m2 and a non-obesity group of 39 patients with BMIs < 28 kg/m2. The medical records of patients were reviewed and all relevant clinical data were further collected into an itemized data spreadsheet for various analyses. RESULTS: Emergent cerclage, along with amnioreduction if needed, could be safely performed on both obese and non-obese pregnant women with a dilated external cervix (> 1 cm), which effectively prolonged the gestational week up to ≥ 25 weeks. Obese gravidae had shorter suture-to-delivery intervals and mean pregnancy lengths but more spontaneous preterm births before 37 weeks, and a lower live birth rate (P < 0.05). Logistic regression analysis revealed that BMI, how many times cerclages have been performed during pregnancy (frequency of cerclage) and bacterial vaginosis, aerobic vaginitis and vulvovaginal candidiasis (vaginal microecology) were significantly correlated with fetal loss (P < 0.05), while rank correlation analysis established a negative correlation between BMI values and the suture-to-delivery interval (P = 0.031). CONCLUSIONS: Pregnant cervical insufficiency patients with BMIs > 28 kg/m2 may ill-serve the gestational outcomes and suture-to-delivery interval after their emergent cerclage. Additionally, BMI, frequency of cerclage and vaginal microecology accounted for higher fetal loss in patients who underwent emergency cerclage.
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Candidiasis Vulvovaginal , Resultado del Embarazo , Embarazo , Recién Nacido , Humanos , Femenino , Índice de Masa Corporal , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Tasa de Natalidad , Obesidad/complicacionesRESUMEN
Microcystis spp., notorious bloom-forming cyanobacteria, are often present in colony form in eutrophic lakes worldwide. Uncovering the mechanisms underlying Microcystis colony formation and maintenance is vital to controlling the blooms, but it has long been a challenge. Here, bacterial communities and gene expression patterns of colonial and unicellular forms of one non-axenic strain of Microcystis aeruginosa isolated from Lake Taihu were compared. Evidently, different microbial communities between them were observed through 16S rDNA MiSeq sequencing. Metatranscriptome analyses revealed that transcripts for pathways involved in bacterial biofilm formation, such as biosynthesis of peptidoglycan and arginine by Bacteroidetes, methionine biosynthesis, alginate metabolism, flagellum, and motility, as well as widespread colonization islands by Proteobacteria, were highly enriched in the colonial form. Furthermore, transcripts for nitrogen fixation and denitrification pathways by Proteobacteria that usually occur in biofilms were significantly enriched in the colonial Microcystis. Results revealed that microbes associated with Microcystis colonies play important roles through regulation of biofilm-related genes in colony formation and maintenance. Moreover, Microcystis colony represents a potential 'buoyant particulate biofilm', which is a good model for biofilm studies. The biofilm features of colonial Microcystis throw a new light on management and control of the ubiquitous blooms in eutrophic waters.
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Microcystis , Alginatos/metabolismo , Arginina/metabolismo , Biopelículas , ADN Ribosómico , Expresión Génica , Lagos/microbiología , Metionina/genética , Metionina/metabolismo , Consorcios Microbianos , Microcystis/metabolismo , Peptidoglicano/metabolismoRESUMEN
Ovarian hormone deprivation is associated with mood disorders, such as depression, and estradiol therapy is significantly more effective than placebos in treating major depression associated with menopause onset. However, the effect of estradiol on neuronal plasticity and its mechanisms remain to be further elucidated. In this study, behavioral assessments were used to examine the antidepressant effect of estradiol in ovariectomized (OVX) B6.Cg-TgN (Thy-YFP-H)-2Jrs transgenic mice on chronic restraint stress (CRS)-induced dendrite and dendritic spine loss; Yellow fluorescent protein (YFP) is characteristically expressed in excitatory neurons in transgenic mice, and its three-dimensional images were used to evaluate the effect of estradiol on the density of different types of dendritic spines. Quantification and distribution of cofilin1 and p-cofilin1 were determined by qPCR, Western blots, and immunohistochemistry, respectively. The results revealed that treatment with estradiol or clomipramine significantly improved depression-like behaviors. Estradiol treatment also significantly upregulated the dendritic density in all areas examined and increased the density of filopodia-type, thin-type and mushroom-type spines in the hippocampal CA1 and elevated the thin-type and mushroom-type spine density in the PFC. Consistent with these changes, estradiol treatment significantly increased the density of p-cofilin1 immunopositive dendritic spines. Thus, these data reveal a possible estradiol antidepressant mechanism, in that estradiol promoted the phosphorylation of cofilin1 and reduced the loss of dendrites and dendritic spines, which of these dendritic spines include not only immature spines such as filopodia-type, but also mature spines such as mushroom-type, and attenuated the depression-like behavior.
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Espinas Dendríticas , Estradiol , Animales , Antidepresivos , Estradiol/farmacología , Femenino , Hipocampo , Ratones , Ratones TransgénicosRESUMEN
Depression afflicts more than 300 million people worldwide, but there is currently no universally effective drug in clinical practice. In this study, chronic restraint stress (CRS)-induced mice depression model was used to study the antidepressant effects of resveratrol and its mechanism. Our results showed that resveratrol significantly attenuated depression-like behavior in mice. Consistent with behavioral changes, resveratrol significantly attenuated CRS-induced reduction in the density of dendrites and dendritic spines in both hippocampus and medial prefrontal cortex (mPFC). Meanwhile, in hippocampus and mPFC, resveratrol consistently alleviated CRS-induced cofilin1 activation by increasing its ser3 phosphorylation. In addition, cofilin1 immunofluorescence distribution in neuronal inner peri-membrane in controls, and cofilin1 diffusely distribution in the cytoplasm in CRS group were common in hippocampus. However, the distribution of cofilin1 in mPFC was reversed. Pearson's correlation analysis revealed that there was a significant positive correlation found between the sucrose consumption in sucrose preference test and the dendrite density in multiple sub-regions of hippocampus and mPFC, and a significant negative correlation between the immobility time in tail suspension test and the dendrite/dendritic spine density in several different areas of hippocampus and mPFC. P-cofilin1 was significantly positively correlated with the overall dendritic spine density in mPFC as well as with the overall dendrite density or BDNF in the hippocampus. Our results suggest that the BDNF/cofilin1 pathway, in which cofilin1 may be activated in a brain-specific manner, was involved in resveratrol's attenuating the dendrite and dendritic spine loss and behavioral abnormality.
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Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cofilina 1/metabolismo , Espinas Dendríticas/efectos de los fármacos , Depresión/tratamiento farmacológico , Resveratrol/uso terapéutico , Animales , Hipocampo/citología , Hipocampo/efectos de los fármacos , Masculino , Ratones Transgénicos , Corteza Prefrontal/citología , Corteza Prefrontal/efectos de los fármacos , Restricción Física , Estrés PsicológicoRESUMEN
Manganese (Mn) is demonstrated to be essential for plants. Ion homeostasis is maintained in plant cells by specialized transporters. PbMTP8.1, which encodes a putative Mn-CDF transporter in Pyrus bretschneideri Rehd, was expressed mainly in leaves and complemented the Mn hypersensitivity of the Mn-sensitive yeast mutant â³pmr1 in previous research conducted by our laboratory. In the present study, we report that the expression of PbMTP8.1 can enhance Mn tolerance and accumulation in Saccharomyces cerevisiae. Subcellular localization analysis of the PbMTP8.1-GFP fusion protein indicated that PbMTP8.1 was targeted to the pre-vacuolar compartment (PVC). In addition, the overexpression of PbMTP8.1 in Arabidopsis thaliana conferred increased resistance to plants under toxic Mn levels, as indicated by increased fresh and dry weights of shoots and roots. Mn accumulation in vacuoles of PbMTP8.1-overexpressing plants was significantly increased when compared with that in wild-type plants under Mn stress. This suggests that a considerable proportion of Mn enters into the vacuoles through a PbMTP8.1-dependent mechanism. Taken together, these results indicate PbMTP8.1 is a Mn-specific transporter that is localized to the PVC, and confers Mn tolerance by sequestering Mn into the vacuole.
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Arabidopsis/metabolismo , Proteínas de Transporte de Catión/genética , Contaminantes Ambientales/toxicidad , Manganeso/toxicidad , Pyrus/metabolismo , Saccharomyces cerevisiae/metabolismo , Adaptación Biológica/genética , Arabidopsis/genética , Contaminantes Ambientales/metabolismo , Manganeso/metabolismo , Células Vegetales/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Pyrus/genética , Saccharomyces cerevisiae/genética , Vacuolas/metabolismoRESUMEN
PM2.5 infiltrates into circulation and increases the risk of systemic vascular dysfunction. As the first-line barrier against external stimuli, the molecular mechanism of the biological response of vascular endothelial cells to PM2.5 exposure remains unclear. In this study, 4-week-old mice were exposed to Hangzhou 'real' airborne PM2.5 for 2 months and were found to display bronchial and alveolar damage. Importantly, in the present study, we have demonstrated that Cdk5 deficit induced peripheral vasoconstriction through angiotensin II type 1 receptor under angiotensin II stimulation in Cdh5-cre;Cdk5f/n mice. In the brain, Cdk5 deficit increased the myogenic activity in the medullary arterioles under external pressure. On the other hand, no changes in cerebral blood flow and behavior patterns were observed in the Cdh5-cre;Cdk5f/n mice exposed to PM2.5. Therefore, our current findings indicate that CDK5 plays an important role in endothelium cell growth, migration, and molecular transduction, which is also a sensor for the response of vascular endothelial cells to PM2.5.
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Contaminantes Atmosféricos/toxicidad , Quinasa 5 Dependiente de la Ciclina/metabolismo , Vasoconstricción/fisiología , Contaminación del Aire , Animales , Encéfalo/metabolismo , Células Endoteliales/metabolismo , Endotelio/metabolismo , Ratones , Receptor de Angiotensina Tipo 1/genética , Activación Transcripcional , Regulación hacia ArribaRESUMEN
BACKGROUND/AIMS: Peptidyl-prolyl cis-trans isomerase FKBP25 is a member of the FK506-binding proteins family which has peptidyl-prolyl cis/trans isomerase domain. The biological function and pathophysiologic role of FKBP25 remain elusive. METHODS: The spatio-temporal changes in expression of endothelial FKBP25 upon oxygen-glucose deprivation (OGD) treatment were examined by Western blot and immunofluorescence. The immunoprecipitation and fluorescence resonance energy transfer (FRET) were used to address the interacting proteins with FKBP25. RESULTS: In the present study, nuclear translocation of FKBP25 was observed following OGD in cultured endothelial cells. Intriguingly, FKBP25 nuclear translocation was further validated in peroxynitrite (ONOO-)-treated endothelial cells. Coimmunoprecipitation and FRET data indicated that FKBP25 translocated into the nucleus, in which it interacted with 60S ribosomal protein L7a, while overexpression FKBP25 protect endothelial cells against OGD injury. CONCLUSION: Our findings reveal that the nuclear import of FKBP25 and binding with 60S ribosomal protein L7a are protective stress responses to ischemia/nitrosaive stress injury.
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Núcleo Celular/metabolismo , Proteínas Ribosómicas/metabolismo , Subunidades Ribosómicas Grandes de Eucariotas/metabolismo , Transducción de Señal , Estrés Fisiológico , Proteínas de Unión a Tacrolimus/metabolismo , Transporte Activo de Núcleo Celular , Animales , Hipoxia de la Célula , RatonesRESUMEN
Phospholipid-mediated signal transduction plays a key role in responses to environmental changes, but little is known about the role of phospholipid signalling in microorganisms. Heat stress (HS) is one of the most important environmental factors. Our previous study found that HS could induce the biosynthesis of the secondary metabolites, ganoderic acids (GA). Here, we performed a comprehensive mass spectrometry-based analysis to investigate HS-induced lipid remodelling in Ganoderma lucidum. In particular, we observed a significant accumulation of phosphatidic acid (PA) on HS. Further genetic tests in which pld-silencing strains were constructed demonstrated that the accumulation of PA is dependent on HS-activated phospholipase D (PLD) hydrolysing phosphatidylethanolamine. Furthermore, we determined the role of PLD and PA in HS-induced secondary metabolism in G. lucidum. Exogenous 1-butanol, which decreased PLD-mediated formation of PA, reverses the increased GA biosynthesis that was elicited by HS. The pld-silenced strains partly blocked HS-induced GA biosynthesis, and this block can be reversed by adding PA. Taken together, our results suggest that PLD and PA are involved in the regulation of HS-induced secondary metabolism in G. lucidum. Our findings provide key insights into how microorganisms respond to heat stress and then consequently accumulate secondary metabolites by phospholipid remodelling.
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Respuesta al Choque Térmico/fisiología , Ácidos Fosfatidicos/metabolismo , Fosfolipasa D/metabolismo , Reishi/metabolismo , Triterpenos/metabolismo , 1-Butanol/farmacología , Activación Enzimática , Calor , Hidrólisis , Fosfatidiletanolaminas/metabolismo , Fosfolipasa D/genética , Interferencia de ARN , Reishi/genética , Metabolismo Secundario , Transducción de SeñalRESUMEN
OBJECTIVE: To investigate the feasibility and diagnostic value of a preoperative transthoracic echocardiography-guided three-dimensional printed model (TTE-guided 3DPM) for the assessment of structural heart disease (SHD). METHODS: Fourty-four patients underwent cardiac surgery at Tianjin Chest Hospital. The patients were preoperatively assessed using TTE-guided 3DPM, which was compared to conventional three-dimensional transthoracic echocardiography (3DTTE) along with direct intraoperative findings, which were considered the "gold standard." Twelve patients had SHD, including four with mitral prolapse, two with partial endocardial cushion defects, two with secondary atrial septal defects, two with rheumatic mitral stenosis, one with tetralogy of Fallot, and one with a ventricular septal defect (VSD). Thirty-two patients who did not have SHDs were designated as the negative control group. RESULTS: The sensitivity and specificity of the TTE-guided 3DPM were greater than or equal to those of the 3DTTE. The P-value of the McNemar test of 3DTTE was >.05, which indicates that the difference was not statistically significant (Kappa = 0.745, P < .001). The P-value of the McNemar test of TTE-guided 3DPM was >.05, which indicates that the difference was not statistically significant (Kappa = 0.955, P < .001). A comparison of 3DTTE and TTE-guided 3DPM resulted in a P-value >.05, which indicates that the difference was not statistically significant (Kappa = 0.879, P < .001). TTE-guided 3DPM displayed the 3D structure of SHDs and cardiac lesions clearly and was consistent with the intra-operative findings. CONCLUSION: Transthoracic echocardiography-guided three-dimensional printed model (TTE-guided 3DPM) provides essential information for preoperative evaluation and decision making for patients with SHDs.
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Ecocardiografía/métodos , Cardiopatías/diagnóstico por imagen , Impresión Tridimensional , Adolescente , Adulto , Anciano , Niño , Preescolar , Ecocardiografía Tridimensional , Estudios de Factibilidad , Femenino , Corazón/diagnóstico por imagen , Corazón/fisiopatología , Cardiopatías/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
The prediction and recognition of promoter in human genome play an important role in DNA sequence analysis. Entropy, in Shannon sense, of information theory is a multiple utility in bioinformatic details analysis. The relative entropy estimator methods based on statistical divergence (SD) are used to extract meaningful features to distinguish different regions of DNA sequences. In this paper, we choose context feature and use a set of methods of SD to select the most effective n-mers distinguishing promoter regions from other DNA regions in human genome. Extracted from the total possible combinations of n-mers, we can get four sparse distributions based on promoter and non-promoters training samples. The informative n-mers are selected by optimizing the differentiating extents of these distributions. Specially, we combine the advantage of statistical divergence and multiple sparse auto-encoders (MSAEs) in deep learning to extract deep feature for promoter recognition. And then we apply multiple SVMs and a decision model to construct a human promoter recognition method called SD-MSAEs. Framework is flexible that it can integrate new feature extraction or new classification models freely. Experimental results show that our method has high sensitivity and specificity.
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Biología Computacional , Genoma Humano , Regiones Promotoras Genéticas , ADN , Humanos , Análisis de Secuencia de ADNRESUMEN
Pathogenic and free-living Acanthamoeba are widely distributed in the environment and have been reported to cause keratitis and universally fatal encephalitis. Primary cutaneous acanthamoebiasis caused by Acanthamoeba is exceedingly rare and presents as isolated necrotic cutaneous lesions without involvement of the cornea or central nervous system. Cutaneous acanthamoebiasis often occurs in immunocompromised patients and is likely overlooked or even misdiagnosed only by cutaneous biopsy tissue histopathological analysis. Here, we report a HIV-infected 63-year-old female with oral leukoplakia for 4 months and scattered large skin ulcers all over the body for 2 months. The cause of the cutaneous lesions was unclear through cutaneous specimens histopathological analysis, and subsequently Acanthamoeba were detected by metagenomic next-generation sequencing (mNGS), which may be the cause of cutaneous lesions. Based on the mNGS results, a pathologist subsequently reviewed the previous pathological slides and found trophozoites of Acanthamoeba so that the cause was identified, and the skin ulcers improved significantly after treatment with multi-drug combination therapy. Acanthamoeba is also a host of pathogenic microorganisms. The presence of endosymbionts enhances the pathogenicity of Acanthamoeba, and no other pathogens were reported in this case. mNGS is helpful for rapidly diagnosing the etiology of rare skin diseases and can indicate the presence or absence of commensal microorganisms.
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Acanthamoeba , Amebiasis , Infecciones por VIH , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Humanos , Femenino , Amebiasis/diagnóstico , Amebiasis/parasitología , Amebiasis/tratamiento farmacológico , Metagenómica/métodos , Persona de Mediana Edad , Acanthamoeba/genética , Acanthamoeba/aislamiento & purificación , Infecciones por VIH/complicaciones , Piel/patología , Piel/parasitología , Resultado del TratamientoRESUMEN
The development of an innovative drug is complex and time-consuming, and the drug target identification is one of the critical steps in drug discovery process. Effective and accurate identification of drug targets can accelerate the drug development process. According to previous research, evolutionary and genetic information of genes has been found to facilitate the identification of approved drug targets. In addition, allosteric proteins have great potential as targets due to their structural diversity. However, this information that could facilitate target identification has not been collated in existing drug target databases. Here, we construct a comprehensive drug target database named Genetic and Evolutionary features of drug Targets database (GETdb, http://zhanglab.hzau.edu.cn/GETdb/page/index.jsp). This database not only integrates and standardizes data from dozens of commonly used drug and target databases, but also innovatively includes the genetic and evolutionary information of targets. Moreover, this database features an effective allosteric protein prediction model. GETdb contains approximately 4000 targets and over 29,000 drugs, and is a user-friendly database for searching, browsing and downloading data to facilitate the development of novel targets.
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Objectives: The aims of this study were to explore the incidence characteristics and trend prediction of lymphoma from 2005 to 2035, and to provide data basis for the prevention and control of lymphoma in China. Method: The data on lymphoma incidence in China from 2005 to 2017 were obtained from the Chinese Cancer Registry Annual Report. The Joinpoint regression model was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to reflect time trends. Age-period-cohort models were conducted to estimate age, period, and cohort effects on the lymphoma incidence. A Bayesian age-period-cohort model was used to predict lymphoma incidence trends from 2018 to 2035. Results: From 2005 to 2017, the incidence of lymphoma was 6.26/100,000, and the age-standardized incidence rate (ASIR) was 4.11/100,000, with an AAPC of 1.4% [95% confidence interval (CI): 0.3%, 2.5%]. The ASIR was higher in men and urban areas than in women and rural areas, respectively. The age effect showed that the incidence risk of lymphoma increased with age. In the period effect, the incidence risk of lymphoma in rural areas decreased first and then increased with 2010 as the cutoff point. The overall risk of lymphoma incidence was higher in the cohort before the 1970-1974 birth cohort than in the cohort after. From 2018 to 2035, the lymphoma incidence in men, women, and urban areas will show an upward trend. Conclusion: From 2005 to 2017, the incidence of lymphoma showed an increasing trend, and was different in regions, genders, and age groups in China. It will show an upward trend from 2018 to 2035. These results are helpful for the formulation and adjustment of lymphoma prevention, control, and management strategies, and have important reference significance for the treatment of lymphoma in China.
RESUMEN
INTRODUCTION: The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions. However, how afferent neurons of mPFC are affected by chronic stress needs to be clarified. In this study, the effects of chronic restraint stress (CRS) on the distribution density of mPFC dendrites/dendritic spines and the projections from the cortex and subcortical brain regions to the mPFC were investigated. METHODS: In the present study, C57BL/6â¯J transgenic (Thy1-YFP-H) mice were subjected to CRS to establish an animal model of depression. The infralimbic (IL) of mPFC was selected as the injection site of retrograde AAV using stereotactic technique. The effects of CRS on dendrites/dendritic spines and afferent neurons of the mPFC IL were investigaed by quantitatively assessing the distribution density of green fluorescent (YFP) positive dendrites/dendritic spines and red fluorescent (retrograde AAV recombinant protein) positive neurons, respectively. RESULTS: The results revealed that retrograde tracing virus labeled neurons were widely distributed in ipsilateral and contralateral cingulate cortex (Cg1), second cingulate cortex (Cg2), prelimbic cortex (PrL), infralimbic cortex, medial orbital cortex (MO), and dorsal peduncular cortex (DP). The effects of CRS on the distribution density of mPFC red fluorescence positive neurons exhibited regional differences, ranging from rostral to caudal or from top to bottom. Simultaneously, CRS resulted a decrease in the distribution density of basal, proximal and distal dendrites, as well as an increase in the loss of dendritic spines of the distal dendrites in the IL of mPFC. Furthermore, varying degrees of red retrograde tracing virus fluorescence signals were observed in other cortices, amygdala, hippocampus, septum/basal forebrain, hypothalamus, thalamus, mesencephalon, and brainstem in both ipsilateral and contralateral brain. CRS significantly reduced the distribution density of red fluorescence positive neurons in other cortices, hippocampus, septum/basal forebrain, hypothalamus, and thalamus. Conversely, CRS significantly increased the distribution density of red fluorescence positive neurons in amygdala. CONCLUSION: Our results suggest a possible mechanism that CRS leads to disturbances in synaptic plasticity by affecting multiple inputs to the mPFC, which is characterized by a decrease in the distribution density of dendrites/dendritic spines in the IL of mPFC and a reduction in input neurons of multiple cortices to the IL of mPFC as well as an increase in input neurons of amygdala to the IL of mPFC, ultimately causing depression-like behaviors.