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RNA polymerase II (RNA Pol II) has been recognized as a passively regulated multi-subunit holoenzyme. However, the extent to which RNA Pol II subunits might be important beyond the RNA Pol II complex remains unclear. Here, fractions containing disassociated RPB3 (dRPB3) were identified by size exclusion chromatography in various cells. Through a unique strategy, i.e., "specific degradation of disassociated subunits (SDDS)," we demonstrated that dRPB3 functions as a regulatory component of RNA Pol II to enable the preferential control of 3' end processing of ribosomal protein genes directly through its N-terminal domain. Machine learning analysis of large-scale genomic features revealed that the little elongation complex (LEC) helps to specialize the functions of dRPB3. Mechanistically, dRPB3 facilitates CBC-PCF11 axis activity to increase the efficiency of 3' end processing. Furthermore, RPB3 is dynamically regulated during development and diseases. These findings suggest that RNA Pol II gains specific regulatory functions by trapping disassociated subunits in mammalian cells.
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RNA Polimerase II , Transcrição Gênica , Animais , RNA Polimerase II/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo , Subunidades Proteicas/genética , Mamíferos/metabolismoRESUMO
RNA polymerase II (RNA Pol II) subunits are thought to be involved in various transcription-associated processes, but it is unclear whether they play different regulatory roles in modulating gene expression. Here, we performed nascent and mature transcript sequencing after the acute degradation of 12 mammalian RNA Pol II subunits and profiled their genomic binding sites and protein interactomes to dissect their molecular functions. We found that RNA Pol II subunits contribute differently to RNA Pol II cellular localization and transcription processes and preferentially regulate RNA processing (such as RNA splicing and 3' end maturation). Genes sensitive to the depletion of different RNA Pol II subunits tend to be involved in diverse biological functions and show different RNA half-lives. Sequences, associated protein factors, and RNA structures are correlated with RNA Pol II subunit-mediated differential gene expression. These findings collectively suggest that the heterogeneity of RNA Pol II and different genes appear to depend on some of the subunits.
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RNA Polimerase II , Splicing de RNA , Animais , RNA Polimerase II/metabolismo , Proteólise , Processamento Pós-Transcricional do RNA , RNA/metabolismo , Transcrição Gênica , Mamíferos/metabolismoRESUMO
BACKGROUND: It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. MAIN BODY: Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1ß (IL-1ß) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. CONCLUSION: Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.
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Becaplermina , Dieta Hiperlipídica , Células Endoteliais , Hipocampo , Síndrome Metabólica , Microglia , Transcitose , Animais , Camundongos , Becaplermina/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Transcitose/fisiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Microglia/metabolismo , Microglia/patologia , Dieta Hiperlipídica/efeitos adversos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Masculino , Osso e Ossos/metabolismo , Osso e Ossos/patologiaRESUMO
Mixed potential ammonia (NH3) sensors with the Fe- and Mo-codoped BiVO4 sensing electrode and Ag reference electrode based on the yttria-stabilized zirconia solid electrolyte were developed. Fe- and Mo-doped BiVO4 sensing materials were prepared using solution combustion synthesis and then characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). It was observed that Fe doping could greatly improve the response rate, while Mo doping could enhance the response signal (ΔU) and sensitivity. Based on the optimal doping ratio of Fe and Mo each, the synergistic enhancement of the performance by Fe and Mo codoping was investigated. The sensor coated by BiV0.75Fe0.2Mo0.05Oδ materials exhibited a prominent sensing performance to a low concentration of 10-50 ppm of NH3 at 525 °C with the outstanding sensitivity of -148.988 mV/decade. Fe and Mo doping also improved the selectivity of the sensor to NH3, with the relative deviations less than ±8% of other typical gases' interference including NO, NO2, CO, CO2, and CH4. Besides, the sensor showed good resistance to fluctuations in the oxygen concentration and favorable stability against changes in the water vapor concentration. In addition, the sensor also exhibited good long-term stability. The mixed potential response mechanism was further discussed and analyzed through polarization curves as well as through gas chromatography and infrared absorption spectroscopy.
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Chromosome Conformation Capture (3C)-based technologies, such as Hi-C, have represented a significant breakthrough in investigating the structure and function of higher-order genome architecture. However, the mapping of global chromatin interactions remains challenging across many biological conditions due to high background noise and financial constraints, especially for small laboratories. Here, we describe the Bridge linker-Alul-Tn5 Hi-C (BAT Hi-C) method, which is a simple and efficient method for delineating chromatin conformational features of mouse embryonic stem (mES) cells and uncover DNA loops. This protocol combines Alul fragmentation and biotinylated linker-mediated proximity ligation to obtain kilobase (kb) resolution with a marked increase in the amount of unique read pairs. The protocol also includes chromatin isolation to reduce background noise and Tn5 tagmentation to cut down on preparation time. Importantly, with only one-third sequencing depth, our method revealed the same spectrum of chromatin contacts as in situ Hi-C. BAT Hi-C is an economical (i.e., approximately $40 for library preparation) and straightforward (total hands-on time of 3â¯days) tool that is ideal for the in-depth analysis of long-range chromatin looping events in a genome-wide fashion.
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Cromatina/genética , Mapeamento Cromossômico/métodos , Genômica/métodos , Animais , Linhagem Celular , Núcleo Celular/genética , Cromatina/isolamento & purificação , Cromatina/metabolismo , Mapeamento Cromossômico/economia , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Células-Tronco Embrionárias , Biblioteca Gênica , Genômica/economia , Camundongos , Transposases/metabolismoRESUMO
Soil amelioration is an effective practice to alleviate the adverse effects of soil salinization. However, increasing the fertility of salt-affected soils has been challenging, particularly in coastal saline-alkaline paddy soils. Here, we carried out a 45-day incubation experiment to evaluate the impacts of soil amendments on fractions and stability of soil organic matter (SOM) in a saline-alkaline paddy. The experiment simulates the flooding-draining practice and consists of CaCO3, gypsum and biochar amendments using different fertility soils. We measured dissolved organic carbon (DOC) and nitrogen (DON) in supernatant liquids, water-soluble cations, water extractable organic carbon (WEOC) and nitrogen (WEON), and microbial biomass carbon (MBC) and nitrogen (MBN) in soils after the incubation. Results showed that water soluble sodium (Na+) was significantly decreased under all amendments (by 17%-32%), except in high fertility soil. We found a significant decrease in DOC (by 36%-47%) under gypsum treatment, but in DON (by 18%-59%) under biochar treatment. However, there was no significant effect on DOC or DON under CaCO3 treatment. Gypsum treatment led to decreased WEOC content (by 0.067%-5.4%), but increased MBC (by 0.16%-44%) and MBN (by 8.3%-37%) in all soils. Biochar treatment caused a decrease in the ratios of WEOC to soil organic carbon (SOC) and WEON to total nitrogen (TN), and an increase in MBC:SOC and MBN:TN ratios. These results suggest that gypsum and biochar amendments can enhance SOM stability in the saline-alkaline paddy. However, SOM stability was not enhanced under CaCO3 treatment, probably due to the presence of a large amount of Na+ in these soils. Our study highlights that soil amelioration has different effects on soil carbon and nitrogen cycles in the saline-alkaline paddy soils, which is associated with water-logged condition.
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Carbono , Solo , Biomassa , Nitrogênio/análise , Microbiologia do SoloRESUMO
BACKGROUND Previous studies demonstrated that tendon-derived stem cells (TDSCs) were vital healing cells and that mRNA expression of anti-inflammatory cytokine IL-6 was significantly upregulated in injured tendons. The aim of the present study was to investigate the effects of IL-6 on the TDSCs in vitro. MATERIAL AND METHODS TDSCs isolated from the Achilles tendons in SD rats were co-cultured with various concentrations of IL-6. Cell proliferation, cell cycle analysis, quantitative real-time PCR, western blotting analysis, and statistical analysis were used in the study. RESULTS The result showed that IL-6 strongly increased proliferation capability, and induced cell cycle activation and transition into G2/M phase from G1 phase in TDSCs. However, IL-6 treatment strongly inhibited gene expression of Scleraxis, Collagen 1, Tenomodulin, Collagen 3, Early Growth Response Protein 1, Decorin, Lumican, Biglycan and Fibromodulin in TDSCs. It also strongly inhibited protein expression of tendon cell markers like scleraxis, collagen 1, collagen 3, and tenomodulin. IL-6 treatment strongly activated the JAK/Stat3 signaling pathway in TDSCs. Furthermore, WP1066, a JAK/Stat3 signaling pathway inhibitor, abrogated the effects of IL-6 on TDSCs. CONCLUSIONS These findings indicated that IL-6 might exert dual effects on TDSCs in vitro: strongly enhancing their proliferation but inhibiting their tenogenic differentiation via the JAK/Stat3 pathway.
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Diferenciação Celular/efeitos dos fármacos , Interleucina-6/farmacologia , Janus Quinases/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/metabolismo , Tendões/citologia , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacosRESUMO
Protein level of Histo-Blood Group ABO System Transferase (BGAT) has been reported to be associated with cardiometabolic diseases. But its effect on pregnancy related outcomes still remains unclear. Here we conducted a two-sample Mendelian randomization (MR) study to ascertain the putative causal roles of protein levels of BGAT in pregnancy related outcomes. Cis-acting protein quantitative trait loci (pQTLs) robustly associated with protein level of BGAT (P < 5 ×10-8) were used as instruments to proxy the BGAT protein level (N = 35,559, data from deCODE), with two additional pQTL datasets from Fenland (N = 10,708) and INTERVAL (N = 3301) used as validation exposures. Ten pregnancy related diseases and complications were selected as outcomes. We observed that a higher protein level of BGAT showed a putative causal effect on venous complications and haemorrhoids in pregnancy (VH) (odds ratio [OR]=1.19, 95% confidence interval [95% CI]=1.12-1.27, colocalization probability=91%), which was validated by using pQTLs from Fenland and INTERVAL. The Mendelian randomization results further showed effects of the BGAT protein on gestational hypertension (GH) (OR=0.97, 95% CI=0.96-0.99), despite little colocalization evidence to support it. Sensitivity analyses, including proteome-wide Mendelian randomization of the cis-acting BGAT pQTLs, showed little evidence of horizontal pleiotropy. Correctively, our study prioritised BGAT as a putative causal protein for venous complications and haemorrhoids in pregnancy. Future epidemiology and clinical studies are needed to investigate whether BGAT can be considered as a drug target to prevent adverse pregnancy outcomes.
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BACKGROUND: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). METHODS: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 µg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a-/-) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. RESULTS: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. CONCLUSIONS: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. SIGNIFICANCE STATEMENT: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.
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Although human core body temperature is known to decrease with age, the age dependency of facial temperature and its potential to indicate aging rate or aging-related diseases remains uncertain. Here, we collected thermal facial images of 2,811 Han Chinese individuals 20-90 years old, developed the ThermoFace method to automatically process and analyze images, and then generated thermal age and disease prediction models. The ThermoFace deep learning model for thermal facial age has a mean absolute deviation of about 5 years in cross-validation and 5.18 years in an independent cohort. The difference between predicted and chronological age is highly associated with metabolic parameters, sleep time, and gene expression pathways like DNA repair, lipolysis, and ATPase in the blood transcriptome, and it is modifiable by exercise. Consistently, ThermoFace disease predictors forecast metabolic diseases like fatty liver with high accuracy (AUC > 0.80), with predicted disease probability correlated with metabolic parameters.
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Envelhecimento , Face , Doenças Metabólicas , Humanos , Pessoa de Meia-Idade , Idoso , Adulto , Masculino , Feminino , Idoso de 80 Anos ou mais , Adulto Jovem , Aprendizado Profundo , Temperatura Corporal , Processamento de Imagem Assistida por ComputadorRESUMO
Stroke is a major threat to life and health in modern society, especially in the aging population. Stroke may cause sudden death or severe sequela-like hemiplegia. Although computed tomography (CT) and magnetic resonance imaging (MRI) are standard diagnosis methods, and artificial intelligence models have been built based on these images, shortage in medical resources and the time and cost of CT/MRI imaging hamper fast detection, thus increasing the severity of stroke. Here, we developed a convolutional neural network model by integrating four networks, Xception, ResNet50, VGG19, and EfficientNetb1, to recognize stroke based on 2D facial images with a cross-validation area under curve (AUC) of 0.91 within the training set of 185 acute ischemic stroke patients and 551 age- and sex-matched controls, and AUC of 0.82 in an independent data set regardless of age and sex. The model computed stroke probability was quantitatively associated with facial features, various clinical parameters of blood clotting indicators and leukocyte counts, and, more importantly, stroke incidence in the near future. Our real-time facial image artificial intelligence model can be used to rapidly screen and prediagnose stroke before CT scanning, thus meeting the urgent need in emergency clinics, potentially translatable to routine monitoring.
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Inteligência Artificial , Face , AVC Isquêmico , Humanos , Masculino , Feminino , AVC Isquêmico/diagnóstico por imagem , Face/diagnóstico por imagem , Idoso , Pessoa de Meia-Idade , Redes Neurais de Computação , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/diagnósticoRESUMO
Abnormal brain-gut interaction is considered the core pathological mechanism behind the disorders of gut-brain interaction (DGBI), in which the intestinal microbiota plays an important role. Microglia are the "sentinels" of the central nervous system (CNS), which participate in tissue damage caused by traumatic brain injury, resist central infection and participate in neurogenesis, and are involved in the occurrence of various neurological diseases. With in-depth research on DGBI, we could find an interaction between the intestinal microbiota and microglia and that they are jointly involved in the occurrence of DGBI, especially in individuals with comorbidities of mental disorders, such as irritable bowel syndrome (IBS). This bidirectional regulation of microbiota and microglia provides a new direction for the treatment of DGBI. In this review, we focus on the role and underlying mechanism of the interaction between gut microbiota and microglia in DGBI, especially IBS, and the corresponding clinical application prospects and highlight its potential to treat DGBI in individuals with psychiatric comorbidities.
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Encefalopatias , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/terapia , Microglia , EncéfaloRESUMO
Tumors managing to exempt from immune clearance are attributable to their overexpressed immune suppressive molecules (CD47, PD-L1, etc.). Leadingly, the checkpoint blockade-based chemoimmunotherapy by means of knockdown of these immunosuppressive checkpoints, together with immunogenetic chemotherapeutics, is perceived to be a valid therapeutic strategy for improving anti-tumor outcomes. Herein, chemotherapeutic camptothecin was covalently introduced into an intriguing multifaceted nanomedicine. Note that the elaborated nanomedicine was chemically engineered to enable targeted transportation to the tumors via systemic administration, possessing intelligent responsiveness to sequential extracellular and intracellular microenvironments in the targeted tumors for prompted transcellular endocytosis owing to enzymolysis by the tumor-enriched matrix metalloproteinases and the selective liberation of cytocidal camptothecin in the cell interiors owing to thiolysis by glutathione. In addition, this chemotherapeutic nanomedicine allowed facile encapsulation of the negatively charged RNA interference payloads. Consequently, aiming for treatment of intractable triple-negative breast tumors, we attempted the small interfering RNA (siRNA) payloads aiming for CD47 and PD-L1 into the aforementioned nanomedicine. The subsequent investigations demonstrated drastic knockdown of these vital immune suppressive checkpoints by this siRNA-encapsulating chemotherapeutic nanomedicine, conducing to the reversal of the immune checkpoint suppressive microenvironment of triple-negative 4T1 tumors. Namely, the inhibited proceedings of the innate and adaptive anti-tumor immunities were revived, as supported by observation of the activated infiltration and retention of CD68+ macrophages and CD4+ and CD8+ lymphocytes into the tumors. Eventually, most potent anti-tumor efficacies were accomplished by systemic administration of this chemoimmunotherapeutic nanomedicine, which verified the amplified contribution from anti-tumor immunities by means of knockdown of the immune suppressive molecules to the ultimate anti-tumor efficacies. Note that the upregulation of the immune suppressive molecules was constantly reported in a variety of clinical therapies; hence, our facile chemoimmunotherapeutic platform should be emphasized in clinical translation for seeking improved therapeutic outcomes.
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Antígeno CD47 , Pró-Fármacos , Antígeno B7-H1 , Pró-Fármacos/farmacologia , Microambiente Tumoral , Nanomedicina , Biomarcadores , Imunoterapia , Linhagem Celular Tumoral , RNA Interferente PequenoRESUMO
Background: We established a diquat-induced human kidney-2 cells (HK-2 cells) apoptosis model in this study to identify differentially expressed microRNAs (miRNAs) and signaling pathways involved in diquat poisoning via gene sequencing and bioinformatics analysis and explored the related therapeutic benefits. Methods: The effects of diquat on the viability and apoptosis of HK-2 cells were explored using the CCK-8 and Annexin V-FITC/PI double staining methods. Total RNAs were extracted using the TRizol method and detected by Illumina HiSeq 2500. Bioinformatics analysis was performed to explore differentially expressed (DE) miRNAs, their enriched biological processes, pathways, and potential target genes. The RT-qPCR method was used to verify the reliability of the results. Results: Diquat led to HK-2 cell injury and apoptosis played an important role, hence an HK-2 cell apoptosis model in diquat poisoning was established. Thirty-six DE miRNAs were screened in diquat-treated HK-2 cells. The enriched biological process terms were mainly cell growth, regulation of apoptotic signaling pathway, extrinsic apoptotic signaling pathway, and Ras protein signal transduction. The enriched cellular components were mainly cell-cell junction, cell-substrate junction, ubiquitin ligase complex, and protein kinase complex. The enriched molecular functions were mainly Ras GTPase binding, ubiquitin-like protein transferase activity, DNA-binding transcription factor binding, ubiquitin-protein transferase activity, nucleoside-triphosphatase regulator activity, transcription coactivator activity, and ubiquitin-like protein ligase binding. Signaling pathways such as MAPK, FoxO, Ras, PIK3-Akt, and Wnt were also enriched. Conclusion: These findings aid in understanding the mechanisms of diquat poisoning and the related pathways, where DE miRNAs serve as targets for gene therapy.
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BACKGROUND: Mammalian cells have three types of RNA polymerases (Pols), Pol I, II, and III. However, the extent to which these polymerases are cross-regulated and the underlying mechanisms remain unclear. RESULTS: We employ genome-wide profiling after acute depletion of Pol I, Pol II, or Pol III to assess cross-regulatory effects between these Pols. We find that these enzymes mainly affect the transcription of their own target genes, while certain genes are transcribed by the other polymerases. Importantly, the most active type of crosstalk is exemplified by the fact that Pol III depletion affects Pol II transcription. Pol II genes with transcription changes upon Pol III depletion are enriched in diverse cellular functions, and Pol III binding sites are found near their promoters. However, these Pol III binding sites do not correspond to transfer RNAs. Moreover, we demonstrate that Pol III regulates Pol II transcription and chromatin binding of the facilitates chromatin transcription (FACT) complex to alter local chromatin structures, which in turn affects the Pol II transcription rate. CONCLUSIONS: Our results support a model suggesting that RNA polymerases show cross-regulatory effects: Pol III affects local chromatin structures and the FACT-Pol II axis to regulate the Pol II transcription rate at certain gene loci. This study provides a new perspective for understanding the dysregulation of Pol III in various tissues affected by developmental diseases.
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Cromatina , RNA Polimerases Dirigidas por DNA , Animais , Transcrição Gênica , RNA Polimerase II , RNA Mensageiro , MamíferosRESUMO
SCOPE: The gut microbiota plays a prominent role in gut-brain interactions and gut dysbiosis is involved in neuroinflammation. However, specific probiotics targeting neuroinflammation need to be explored. In this study, the antineuroinflammatory effect of the potential probiotic Roseburia hominis (R. hominis) and its underlying mechanisms is investigated. METHODS AND RESULTS: First, germ-free (GF) rats are orally treated with R. hominis. Microglial activation, proinflammatory cytokines, levels of short-chain fatty acids, depressive behaviors, and visceral sensitivity are assessed. Second, GF rats are treated with propionate or butyrate, and microglial activation, proinflammatory cytokines, histone deacetylase 1 (HDAC1), and histone H3 acetyl K9 (Ac-H3K9) are analyzed. The results show that R. hominis administration inhibits microglial activation, reduces the levels of IL-1α, INF-γ, and MCP-1 in the brain, and alleviates depressive behaviors and visceral hypersensitivity in GF rats. Moreover, the serum levels of propionate and butyrate are increased significantly in the R. hominis-treated group. Propionate or butyrate treatment reduces microglial activation, the levels of proinflammatory cytokines and HDAC1, and promotes the expression of Ac-H3K9 in the brain. CONCLUSION: These findings suggest that R. hominis alleviates neuroinflammation by producing propionate and butyrate, which serve as HDAC inhibitors. This study provides a potential psychoprobiotic to reduce neuroinflammation.
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Eixo Encéfalo-Intestino , Butiratos , Clostridiales , Ácidos Graxos Voláteis , Histona Desacetilase 1 , Doenças Neuroinflamatórias , Probióticos , Propionatos , Animais , Butiratos/sangue , Butiratos/metabolismo , Clostridiales/metabolismo , Citocinas/metabolismo , Ácidos Graxos Voláteis/metabolismo , Vida Livre de Germes , Histona Desacetilase 1/metabolismo , Histonas/metabolismo , Doenças Neuroinflamatórias/terapia , Probióticos/uso terapêutico , Propionatos/sangue , Propionatos/metabolismo , RatosRESUMO
Dynamic semiconductor diode generators (DDGs) offer a potential portable and miniaturized energy source, with the advantages of high current density, low internal impedance, and independence of the rectification circuit. However, the output voltage of DDGs is generally as low as 0.1-1 V, owing to energy loss during carrier transport and inefficient carrier collection, which requires further optimization and a deeper understanding of semiconductor physical properties. Therefore, this study proposes a vertical graphene/silicon DDG to regulate the performance by realizing hot carrier transport and collection. With instant contact and separation of the graphene and silicon, hot carriers are generated by the rebounding process of built-in electric fields in dynamic graphene/silicon diodes, which can be collected within the ultralong hot electron lifetime of graphene. In particular, monolayer graphene/silicon DDG outputs a high voltage of 6.1 V as result of ultrafast carrier transport between the monolayer graphene and silicon. Furthermore, a high current of 235.6 nA is generated due to the carrier multiplication in graphene. A voltage of 17.5 V is achieved under series connection, indicating the potential to supply electronic systems through integration design. The graphene/silicon DDG has applications as an in situ energy source for harvesting mechanical energy from the environment.
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Medical image segmentation is an essential component of computer-aided diagnosis (CAD) systems. Thyroid nodule segmentation using ultrasound images is a necessary step for the early diagnosis of thyroid diseases. An encoder-decoder based deep convolutional neural network (DCNN), like U-Net architecture and its variants, has been extensively used to deal with medical image segmentation tasks. In this article, we propose a novel N-shape dense fully convolutional neural network for medical image segmentation, referred to as N-Net. The proposed framework is composed of three major components: a multi-scale input layer, an attention guidance module, and an innovative stackable dilated convolution (SDC) block. First, we apply the multi-scale input layer to construct an image pyramid, which achieves multi-level receiver field sizes and obtains rich feature representation. After that, the U-shape convolutional network is employed as the backbone structure. Moreover, we use the attention guidance module to filter the features before several skip connections, which can transfer structural information from previous feature maps to the following layers. This module can also remove noise and reduce the negative impact of the background. Finally, we propose a stackable dilated convolution (SDC) block, which is able to capture deep semantic features that may be lost in bilinear upsampling. We have evaluated the proposed N-Net framework on a thyroid nodule ultrasound image dataset (called the TNUI-2021 dataset) and the DDTI publicly available dataset. The experimental results show that our N-Net model outperforms several state-of-the-art methods in the thyroid nodule segmentation tasks.
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BACKGROUND AND OBJECTIVE: A thyroid nodule is an abnormal lump that grows in the thyroid gland, which is the early symptom of thyroid cancer. In order to diagnose and treat thyroid cancer at the earliest stage, it is desired to characterize the nodule accurately. Ultrasound thyroid nodules segmentation is a challenging task due to the speckle noise, intensity heterogeneity, low contrast and low resolution. In this paper, we propose a novel framework to improve the accuracy of thyroid nodules segmentation. METHODS: Different from previous work, a super-resolution reconstruction network is firstly constructed to upscale the resolution of the input ultrasound image. After that, our proposed N-shape network is utilized to perform the segmentation task. The guidance of super-resolution reconstruction network can make the high-frequency information of the input thyroid ultrasound image richer and more comprehensive than the original image. Our N-shape network consists of several atrous spatial pyramid pooling blocks, a multi-scale input layer, a U-shape convolutional network with attention blocks and a proposed parallel atrous convolution(PAC) module. These modules are conducive to capture context information at multiple scales so that semantic features can be fully utilized for lesion segmentation. Especially, our proposed PAC module is beneficial to further improve the segmentation by extracting high-level semantic features from different receptive fields. We use the UTNI-2021 dataset for model training, validating and testing. RESULTS: The experimental results show that our proposed method achieve a Dice value of 91.9%, a mIoU value of 87.0%, a Precision value of 88.0%, a Recall value 83.7% and a F1-score value of 84.3%, which outperforms most state-of-the-art methods. CONCLUSIONS: Our method achieves the best performance on the UTNI-2021 dataset and provides a new way of ultrasound image segmentation. We believe that our method can provide doctors with reliable auxiliary diagnosis information in clinical practice.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Ultrassonografia/métodosRESUMO
Somatostatin-positive (SOM+) neurons have been proposed as one of the key populations of excitatory interneurons in the spinal dorsal horn involved in mechanical pain. However, the molecular mechanism for their role in pain modulation remains unknown. Here, we showed that the T-type calcium channel Cav3.2 was highly expressed in spinal SOM+ interneurons. Colocalization of Cacna1h (which codes for Cav3.2) and SOM tdTomato was observed in the in situ hybridization studies. Fluorescence-activated cell sorting of SOM tdTomato cells in spinal dorsal horn also proved a high expression of Cacna1h in SOM+ neurons. Behaviorally, virus-mediated knockdown of Cacna1h in spinal SOM+ neurons reduced the sensitivity to light touch and responsiveness to noxious mechanical stimuli in naïve mice. Furthermore, knockdown of Cacna1h in spinal SOM+ neurons attenuated thermal hyperalgesia and dynamic allodynia in the complete Freund's adjuvant-induced inflammatory pain model, and reduced both dynamic and static allodynia in a neuropathic pain model of spared nerve injury. Mechanistically, a decrease in the percentage of neurons with Aß-eEPSCs and Aß-eAPs in superficial dorsal horn was observed after Cacna1h knockdown in spinal SOM+ neurons. Altogether, our results proved a crucial role of Cav3.2 in spinal SOM+ neurons in mechanosensation under basal conditions and in mechanical allodynia under pathological pain conditions. This work reveals a molecular basis for SOM+ neurons in transmitting mechanical pain and shows a functional role of Cav3.2 in tactile and pain processing at the level of spinal cord in addition to its well-established peripheral role.