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OBJECTIVE: To assess the impact of vertical integration (VI) within County-Level Integrated Health Organisations (CIHOs) on the costs of primary care inpatients. METHODS: This study assessed Xishui, a national pilot county for CIHOs, using inpatient claims data. The treatment group comprised 10,118 inpatients from 5 vertically integrated township health centres (THCs), while the control group consisted of 21,165 inpatients from 19 non-vertically integrated THCs. The periods from July 2020 to December 2021 and January 2022 to December 2022 were defined as pre- and post-policy intervention, respectively. The primary outcome variables were total health expenditures (THS), out-of-pocket (OOP) expenditures, and the proportion of OOP expenditures. Propensity score matching was employed to align inpatient demographics and disease characteristics between the groups, followed by a difference-in-differences analysis to evaluate the outcomes. FINDINGS: VI significantly increased THS (ß = 0.1337, p < 0.01) and OOP expenditures per case (ß = 0.1661, p < 0.001), but the increase in the proportion of OOP expenditures per case was not significant (ß = 0.0029, p > 0.05). For the basic medical insurance for urban and rural residents, THS per case (ß = 0.1343, p < 0.01) and OOP expenditures (ß = 0.1714, p < 0.001) significantly increased. For the basic medical insurance system for employees, THS per case also increased significantly (ß = 0.1238, p < 0.01), but the change in OOP expenditure proportion per case was not significant (ß = 0.1020, p > 0.05). The THS per case led by Xishui County People's Hospital, the leading county medical sub-centre (CMSC), significantly increased (ß = 0.1753, p < 0.01), whereas the increase led by Xishui County Traditional Chinese Medicine Hospital was not significant (ß = 0.0742, p > 0.05). Increases in OOP expenditures per case were significant in CMSCs led by the People's Hospital and the Traditional Chinese Medicine Hospital (ß = 0.1782, p < 0.01 and ß = 0.0757, p < 0.05, respectively). CONCLUSION: VI significantly increased THS and OOP expenditures for primary care inpatients. However, VI could exacerbate economic disparities in disease burden across different insurance categories.
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The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.
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AIMS: To establish a system based on hyperspectral imaging and deep learning for the detection of cancer cells in metastatic lymph nodes. MAIN METHODS: The continuous sections of metastatic lymph nodes from 45 oral squamous cell carcinoma (OSCC) patients were collected. An improved ResUNet algorithm was established for deep learning to analyze the spectral curve differences between cancer cells and lymphocytes, and that between tumor tissue and normal tissue. KEY FINDINGS: It was found that cancer cells, lymphocytes, and erythrocytes in the metastatic lymph nodes could be distinguished basing hyperspectral image, with overall accuracy (OA) as 87.30% and average accuracy (AA) as 85.46%. Cancerous area could be recognized by hyperspectral image and deep learning, and the average intersection over union (IOU) and accuracy were 0.6253 and 0.7692, respectively. SIGNIFICANCE: This study indicated that deep learning-based hyperspectral techniques can identify tumor tissue in OSCC metastatic lymph nodes, achieving high accuracy of pathological diagnosis, high work efficiency, and reducing work burden. But these are preliminary results limited to a small sample.
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OBJECTIVES: Tumor metastasis is a primary cause of recurrence and mortality in endometrial cancer. miR-34b-5p is abnormally expressed in various cancers and participates in tumor cell progression and metastasis. The objective of this study was to elucidate the biological functions and molecular mechanisms of miR-34b-5p in regulating the epithelial-mesenchymal transition (EMT) and metastasis in AN3CA endometrial cancer cells. METHODS: The expression levels of miR-34b-5p and zinc finger E-box-binding homeobox 1 (ZEB1) in endometrial cancer cells were analyzed by qRT-PCR, and ZEB1 expression in endometrial cancer tissues was examined by immunohistochemistry. Proliferation, migration, and invasion of endometrial cancer AN3CA cells were evaluated using CCK8, scratch, and transwell assays, respectively. Bioinformatic analysis and dual-luciferase reporter gene assays were used to validate the targeting relationship between miR-34b-5p and ZEB1. Western blotting was performed to analyze the expression levels of ZEB1 and EMT-related proteins. RESULTS: miR-34b-5p was significantly downregulated in endometrial cancer AN3CA cells. Overexpression of miR-34b-5p significantly inhibited proliferation, invasion, migration, and the EMT of endometrial cancer AN3CA cells. ZEB1, which was identified as a direct target gene of miR-34b-5p, exhibited high expression in endometrial cancer cells and tissues. Additionally, ZEB1 upregulation partially reversed the inhibitory effects of miR-34b-5p on proliferation, migration, invasion, and the EMT of endometrial cancer AN3CA cells. CONCLUSIONS: miR-34b-5p suppresses the EMT and metastasis in endometrial cancer AN3CA cells by targeting ZEB1, indicating that the miR-34b-5p-ZEB1-EMT axis may be a therapeutic target for endometrial cancer.
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Epstein-Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1's crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.
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Antígenos de Diferenciación , Efrina-A2 , Células Epiteliales , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Receptor EphA2 , Internalización del Virus , Humanos , Herpesvirus Humano 4/fisiología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Células Epiteliales/virología , Células Epiteliales/metabolismo , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/metabolismo , Receptor EphA2/metabolismo , Efrina-A2/metabolismo , Efrina-A2/genética , Antígenos de Diferenciación/metabolismo , Antígenos de Diferenciación/genética , Animales , Células HEK293 , Unión Proteica , Ratones , Línea CelularRESUMEN
Oral squamous cell carcinoma (OSCC) has the characteristics of early regional lymph node metastasis. OSCC patients often have poor prognoses and low survival rates due to cervical lymph metastases. Therefore, it is necessary to rely on a reasonable screening method to quickly judge the cervical lymph metastastic condition of OSCC patients and develop appropriate treatment plans. In this study, the widely used pathological sections with hematoxylin-eosin (H&E) staining are taken as the target, and combined with the advantages of hyperspectral imaging technology, a novel diagnostic method for identifying OSCC lymph node metastases is proposed. The method consists of a learning stage and a decision-making stage, focusing on cancer and non-cancer nuclei, gradually completing the lesions' segmentation from coarse to fine, and achieving high accuracy. In the learning stage, the proposed feature distillation-Net (FD-Net) network is developed to segment the cancerous and non-cancerous nuclei. In the decision-making stage, the segmentation results are post-processed, and the lesions are effectively distinguished based on the prior. Experimental results demonstrate that the proposed FD-Net is very competitive in the OSCC hyperspectral medical image segmentation task. The proposed FD-Net method performs best on the seven segmentation evaluation indicators: MIoU, OA, AA, SE, CSI, GDR, and DICE. Among these seven evaluation indicators, the proposed FD-Net method is 1.75%, 1.27%, 0.35%, 1.9%, 0.88%, 4.45%, and 1.98% higher than the DeepLab V3 method, which ranks second in performance, respectively. In addition, the proposed diagnosis method of OSCC lymph node metastasis can effectively assist pathologists in disease screening and reduce the workload of pathologists.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello , Metástasis Linfática/diagnóstico por imagen , Neoplasias de la Boca/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagenRESUMEN
BACKGROUND: Cellular response to pharmacological action of drugs is significant for drug development. Traditional detection method for cellular response to drugs normally rely on cell proliferation assay and metabolomics examination. In principle, these analytical methods often required cell labeling, invasion analysis, and hours of co-culture with drugs, which are relatively complex and time-consuming. Moreover, these methods can only indicate the drug effectiveness on cell colony rather than single cells. Thus, to meet the requirements of personal precision medicine, the development of drug response analysis on the high resolution of single cell is demanded. RESULTS: To provide precise result for drug response on single-cell level, a microfluidic platform coupled with the label-free hyperspectral imaging was developed. With the help of horizontal single-cell trapping sieves, hundreds of single cells were trapped independently in microfluidic channels for the purposes of real-time drug delivery and single-cell hyperspectral image recording. To significantly identify the cellular hyperspectral change after drug stimulation, the differenced single-cell spectrum was proposed. Compared with the deep learning classification method based on hyperspectral images, an optimal performance can be achieved by the classification strategy based on differenced spectra. And the cellular response to different reagents, for example, K+, Epidermal Growth Factor (EGF), and Gefitinib at different concentrations can be accurately characterized by the differenced single-cell spectra analysis. SIGNIFICANCE AND NOVELTY: The high-throughput, rapid analysis of cellular response to drugs at the single-cell level can be accurately performed by our platform. After systematically analyzing the materials and the structures of the single-cell microfluidic chip, the optimal single-cell trapping method was proposed to contribute to the further application of hyperspectral imaging on microfluidic single-cell analysis. And the hyperspectral characterization of single-cell with cancer drug stimulation proved the application potential of our method in personal cancer medication.
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Imágenes Hiperespectrales , Microfluídica , Microfluídica/métodos , Preparaciones Farmacéuticas , Técnicas de Cocultivo , Análisis de la Célula IndividualRESUMEN
The discernible alterations in regional precipitation patterns, influenced by the intersecting factors of urbanization and climate change, exert a substantial impact on urban flood disasters. Based on multi-source precipitation data, a data-driven model fusion framework was constructed to analyze the spatial and temporal dynamic distribution characteristics of precipitation in Beijing. Wavelet analysis method was used to reveal the periodic variation characteristics and multi-scale effects of precipitation, and the machine learning method was used to characterize the spatiotemporal dynamic change pattern of precipitation. Finally, geographical detector was used to explore the causes of waterlogging in Beijing. The research outcomes reveal a disparate distribution of precipitation across the year, with 78 % of the total precipitation occurring during the flood season. The principal periodic cycles observed in annual cumulative precipitation (ACP) were identified at 21, 13, and 9-year intervals. Spatially, while a decreasing trend in precipitation was observed in most areas of Beijing, 63.4 % of the region exhibited an escalating concentration trend, thereby heightening the risk of urban waterlogging. Machine learning model clustering elucidated three predominant spatial dynamic distribution patterns of precipitation in Beijing. The utilization of web crawler technology to acquire water accumulation data addressed challenges in obtaining urban waterlogging data, and validation through Landsat8 images enhanced data reliability and authenticity. Factor detection shows that road network density, topography, and precipitation were the main factors affecting urban waterlogging. These findings hold significant implications for informing flood control strategies and emergency management protocols in urban areas across China.
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Isodon rubescens has garnered much attention due to its anti-tumor or anti-cancer properties. However, little is known about the molecular mechanism of oridonin biosynthesis leveraging the regulatory network between small RNAs and mRNAs. In this study, the regulatory networks of miRNAs and targets were examined by combining mRNA, miRNA, and degradome. A total of 348 miRNAs, including 287 known miRNAs and 61 novel miRNAs, were identified. Among them, 51 miRNAs were significantly expressed, and 36 miRNAs responded to MeJA. A total of 3066 target genes were associated with 228 miRNAs via degradome sequencing. Multi-omics analysis demonstrated that 27 miRNA-mRNA pairs were speculated to be involved in MeJA regulation, and 36 miRNA-mRNA pairs were hypothesized to be involved in the genotype-dependence of I. rubescens. Furthermore, 151 and 7 miRNA-mRNA modules were likely engaged in oridonin biosynthesis as identified by psRNATarget and degradome sequencing, respectively. Some miRNA-mRNA modules were confirmed via RT-qPCR. Moreover, miRNAs targeting plant hormone signal transduction pathway genes were identified, such as miR156, miR167, miR393, and PC-3p-19822_242. Collectively, our results demonstrate for the first time that miRNAs are identified in I. rubescens, and laid a solid foundation for further research on the molecular mechanism of oridonin biosynthesis mediated by miRNA.
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Diterpenos de Tipo Kaurano , Isodon , MicroARNs , MicroARNs/genética , Isodon/genética , Isodon/metabolismo , Multiómica , Transcriptoma , ARN Mensajero/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
The propagation of cultivated garlic relies on vegetative cloves, thus flowers become non-essential for reproduction in this species, driving the evolution of reproductive feature-derived traits. To obtain insights into the evolutionary alteration of reproductive traits in the clonally propagated garlic, the evolutionary histories of two main reproduction-related traits, bolting and flower differentiation, were explored by genome analyses using 134 accessions displaying wide diversity in these two traits. Resequencing identified 272.8 million variations in the garlic genome, 198.0 million of which represent novel variants. Population analysis identified five garlic groups that have evolved into two clades. Gene expression, single-cell transcriptome sequencing, and genome-wide trait association analyses have identified numerous candidates that correlate with reproductive transition and flower development, some of which display distinct selection signatures. Selective forces acting on the B-box zinc finger protein-encoding Asa2G00291.1, the global transcription factor group E protein-encoding Asa5G01527.1, and VERNALIZATION INSENSITIVE 3-like Asa3G03399.1 appear to be representative of the evolution of garlic bolting. Plenty of novel genomic variations and trait-related candidates represent valuable resources for biological studies of garlic. Numerous selective signatures from genes associated with the two chosen reproductive traits provide important insights into the evolutionary history of reproduction in this clonally propagated crop.
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Boron-doped diamond (BDD) thin film electrodes have great application potential in water treatment. However, the high electrode energy consumption due to high resistance directly limits the application range of existing BDD electrodes. In this paper, the BDD/graphene/BDD (DGD) sandwich structure electrode was prepared, which effectively improved the conductivity of the electrode. Meanwhile, the sandwich electrode can effectively avoid the degradation of electrode performance caused by the large amount of non-diamond carbon introduced by heavy doping, such as the reduction of the electrochemical window and the decrease of physical and chemical stability. The microstructure and composition of the film were characterized by scanning electron microscope (SEM), atomic force microscopy (AFM), Raman spectroscopy, and transmission electron microscopy (TEM). Then, the degradation performance of citric acid (CA), catechol, and tetracycline hydrochloride (TCH) by DGD electrodes was systematically studied by total organic carbon (TOC) and Energy consumption per unit TOC removal (ECTOC). Compared with the single BDD electrode, the new DGD electrode improves the mobility of the electrode and reduces the mass transfer resistance by 1/3, showing better water treatment performance. In the process of dealing with Citric acid, the step current of the DGD electrode was 1.35 times that of the BDD electrode, and the energy utilization ratio of the DGD electrode was 2.4 times that of the BDD electrode. The energy consumption per unit TOC removal (ECTOC) of the DGD electrode was lower than that of BDD, especially Catechol, which was reduced to 66.9% of BDD. The DGD sandwich electrode, as a new electrode material, has good electrochemical degradation performance and can be used for high-efficiency electrocatalytic degradation of organic pollutants.
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Nanoparticles are usually used as carrier to load more antibody and enzyme to improve the sensitivity of enzyme-linked immunosorbent assay (ELISA). However, limited by high density and complicated modification procedure, the traditional nanoparticles such as Au nanoparticles (AuNPs) usually induce large background signal and poor reproducibility in ELISA. In this work, functional lightweigh nanoparticle polystyrene@polydopamine (PS@PDA) was prepared and induced as the carrier of detection antibody and horseradish peroxidase (HRP) to form PS@PDA@Ab2/HRP biojungates. The appropriate density (close to water) and good hydropilicity ensure the good dispersion of PS@PDA@Ab2/HRP in solution, preventing the physical sedimention and decreasing the background signal even though the bioconjugate's size is close to 200 nm. The large surface area and abundant active group from PDA facilitate the loading of detection antibody and HRP, improving the loading efficiency and stability of biojungates. Based on it, taking interleukin-17A (IL-17A, a biomarker of psoriasis) as the detection target, we developed a PS@PDA-based sandwich ELISA, achieving a sensitive dynamic range from 0.3 to 80 pg/mL and a detection limit of 0.2 pg/mL. Furthermore, the contents of IL-17A were assayed successfully in 10-fold diluted serum samples from psoriasis patients. Compared with those commercial or AuNP-based ELISA, our PS@PDA-based ELISA method exhibits higher sensitivity, lower background interference, and higher stability, which will significantly improve the application of ELISA in the low-abundant biomolecule assays.
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Técnicas Biosensibles , Nanopartículas del Metal , Psoriasis , Humanos , Oro , Poliestirenos , Interleucina-17 , Reproducibilidad de los Resultados , Ensayo de Inmunoadsorción Enzimática , Peroxidasa de Rábano Silvestre , Anticuerpos , Técnicas Biosensibles/métodosRESUMEN
BACKGROUND: Garlic is an entirely sterile crop with important value as a vegetable, condiment, and medicine. However, the evolutionary history of garlic remains largely unknown. RESULTS: Here we report a comprehensive map of garlic genomic variation, consisting of amazingly 129.4 million variations. Evolutionary analysis indicates that the garlic population diverged at least 100,000 years ago, and the two groups cultivated in China were domesticated from two independent routes. Consequently, 15.0 and 17.5% of genes underwent an expression change in two cultivated groups, causing a reshaping of their transcriptomic architecture. Furthermore, we find independent domestication leads to few overlaps of deleterious substitutions in these two groups due to separate accumulation and selection-based removal. By analysis of selective sweeps, genome-wide trait associations and associated transcriptomic analysis, we uncover differential selections for the bulb traits in these two garlic groups during their domestication. CONCLUSIONS: This study provides valuable resources for garlic genomics-based breeding, and comprehensive insights into the evolutionary history of this clonal-propagated crop.
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Ajo , Ajo/genética , Genoma de Planta , Genómica , Fitomejoramiento , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Rapid laboratory technologies which can effectively distinguish active tuberculosis (ATB) from controls and latent tuberculosis infection (LTBI) are lacked.The objective of this study is to explore MTB biomarkers in serum that can distinguish ATB from LTBI. METHODS: We constructed a tuberculosis protein microarray containing 64 MTB associated antigens. We then used this microarray to screen 180 serum samples, from patients with ATB and LTBI, and healthy volunteer controls. Both SAM (Significance analysis of microarrays) and ROC curve analysis were used to identify the differentially recognized biomarkers between groups. Extra 300 serum samples from patients with ATB and LTBI, and healthy volunteer controls were employed to validate the identified biomarkers using ELISA-based method. RESULTS: According to the results, the best biomarker combinations of 4 proteins (Rv1860, RV3881c, Rv2031c and Rv3803c) were selected. The biomarker panel containing these 4 proteins has reached a sensitivity of 93.3% and specificity of 97.7% for distinguishing ATB from LTBI, and a sensitivity of 86% and specificity of 97.6% for distinguishing ATB from HC. CONCLUSION: The biomarker combination in this study has high sensitivity and specificity in distinguishing ATB from LTBI, suggesting it is worthy for further validation in more clinical samples.
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Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis Latente/diagnóstico , Análisis por Matrices de Proteínas , Sensibilidad y Especificidad , BiomarcadoresRESUMEN
GRAS transcription factors play crucial roles in plant growth and development and have been widely explored in many plant species. Garlic (Allium sativum L.) is an important crop owing to its edible and medicinal properties. However, no GRAS transcription factors have been identified in this crop. In this study, 46 garlic GRAS genes were identified and assigned to 16 subfamilies using the GRAS members of Arabidopsis thaliana, Oryza sativa, and Amborella trichopoda as reference queries. Expression analysis revealed that garlic GRAS genes showed distinct differences in various garlic tissues, as well as during different growth stages of the bulbs. Five of these 46 genes were identified as DELLA-like protein-encoding genes and three of which, Asa2G00237.1/Asa2G00240.1 and Asa4G02090.1, responded to exogenous GA3 treatment, and showed a significant association between their transcription abundance and bulb traits in 102 garlic accessions, thereby indicating their role in regulating the growth of garlic bulbs. These results will lay a useful foundation for further investigation of the biological functions of GRAS genes and guiding the genetic breeding of garlic in the future.
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Isodon rubescens (Hemsley) H. Hara (Lamiaceae) is a traditional Chinese medicine plant that has been used to treat various human diseases and conditions such as inflammation, respiratory and gastrointestinal bacterial infections, and malignant tumors. However, the contents of the main active components of I. rubescens from different origins differ significantly, which greatly affected its quality. Therefore, a molecular method to identify and classify I. rubescens is needed. Here, we report the DNA sequence of the chloroplast genome of I. rubescens collected from Lushan, Henan province. The genome is 152,642 bp in length and has a conserved structure that includes a pair of IR regions (25,726 bp), a LSC region (83,527 bp) and a SSC region (17,663 bp). The chloroplast genome contains 113 unique genes, four rRNA genes, 30 tRNA genes, and 79 protein-coding genes, 23 of which contain introns. The protein-coding genes account for a total of 24,412 codons, and most of them are A/T biased usage. We identified 32 simple sequence repeats (SSRs) and 48 long repeats. Furthermore, we developed valuable chloroplast molecular resources by comparing chloroplast genomes from three Isodon species, and both mVISTA and DnaSP analyses showed that rps16-trnQ, trnS-trnG, and ndhC-trnM are candidate regions that will allow the identification of intraspecific differences within I. rubescens. Also 14 candidate fragments can be used to identify interspecific differences between species in Isodon. A phylogenetic analysis of the complete chloroplast genomes of 24 species in subfamily Nepetoideae was performed using the maximum likelihood method, and shows that I. rubescens clustered closer to I. serra than I. lophanthoides. Interestingly, our analysis showed that I. rubescens (MW018469.1) from Xianyang, Shaanxi Province (IR-X), is closer to I. serra than to the other two I. rubescens accessions. These results strongly indicate that intraspecific diversity is present in I. rubescens. Therefore, our results provide further insight into the phylogenetic relationships and interspecific diversity of species in the genus Isodon.
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Genoma del Cloroplasto , Isodon , Plantas Medicinales , Humanos , Isodon/genética , Repeticiones de Microsatélite/genética , Filogenia , Plantas Medicinales/genéticaRESUMEN
In this study, we constructed and annotated a complete circular chloroplast genome of wild R. glutinosa. The chloroplast genome of wild R. glutinosa is 153,678 bp in length, including two inverted repeat (IR) regions of 25,759 bp, separated by a large single copy (LSC) region of 84,544 bp and a small single copy (SSC) region of 17,616 bp. The genome contains 149 genes, including 104 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Neighbor-joining method phylogenomic analysis showed that wild R. glutinosa formed a monophyletic group, and was sister to other groups of R. glutinosa.
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It is challenging to increase the sensitivity of a hydrogen sensor operating at room temperature due to weak sorption and tiny mass of hydrogen. In this work, an ultrasonic sensor is presented for detecting hydrogen, which is composed of a 128° YX-LiNbO3 substrate and a reduced graphene oxide (RGO) sensitive layer with a platinum catalyzer. By optimizing the depositing parameters of RGO and platinum, a considerably high sensitivity is achieved at room temperature. A frequency shift of 308.9 kHz is obtained in 100 ppm hydrogen mixed with argon, and a frequency shift of 24.4 kHz is obtained in 1000 ppm hydrogen mixed in synthetic air. It is demonstrated that in addition to strong sorption of the sensitive layer, the coaction of mass load and conductivity variation is key to high sensitivity of the sensor. By establishing the original conductivity of the sensitive layer within the "conductivity window" for enhancing electrical response, we improve the sensitivity of the ultrasonic sensor, which is available for detecting hydrogen with an extremely low concentration of 5 ppm.
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Pulmonary fibrosis (PF), which is characterized by excessive matrix formation, may ultimately lead to irreversible lung damage and thus death. Fibroblast activation has been regarded as a central event during PF pathogenesis. In our previous study, we confirmed that the miR-627/high-mobility group box protein 1 (HMGB1)/Nuclear factor kappa beta (NF-κB) axis modulates transforming growth factor beta 1 (TGFß1)-induced pulmonary fibrosis. In the present study, we investigated the upstream factors leading to miR-627 dysregulation in the process of pulmonary fibroblast activation and PF. The lncRNA MIR155 host gene (MIR155HG) was found to be abnormally upregulated in pulmonary fibrosis tissues and TGFß1-stimulated normal human primary lung fibroblasts (NHLFs). By directly binding to miR-627, MIR155HG inhibited miR-627 expression. MIR155HG overexpression enhanced TGFß1-induced increases in HMGB1 protein expression and p65 phosphorylation, NHLF proliferation, and extracellular matrix (ECM) deposition. In contrast, miR-627 overexpression attenuated the TGFß1-induced changes in NHLFs and significantly reversed the effects of MIR155HG overexpression. Under TGFß1 stimulation, miR-627 inhibition promoted, whereas JSH-23 treatment inhibited NF-κB activation; in NHLFs, NF-κB overexpression upregulated, whereas JSH-23 treatment downregulated MIR155HG expression. In tissue samples, HMGB1 protein levels and p65 phosphorylation were increased; MIR155HG was negatively correlated with miR-627 and positively correlated with HMGB1. In conclusion, we validated that the MIR155HG/miR-627/HMGB1/NF-κB axis formed a regulatory loop that modulates TGFß1-induced NHLF activation. Considering the critical role of NHLF activation in PF pathogenesis, the NF-κB/MIR155HG/miR-627/HMGB1 regulatory loop could exert a vital effect on PF pathogenesis. Further in vivo and clinical investigations are required to confirm this model.
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Matriz Extracelular/metabolismo , Fibroblastos/citología , Proteína HMGB1/metabolismo , MicroARNs/genética , FN-kappa B/metabolismo , Fibrosis Pulmonar/patología , ARN Largo no Codificante/genética , Estudios de Casos y Controles , Proliferación Celular , Fibroblastos/metabolismo , Regulación de la Expresión Génica , Proteína HMGB1/genética , Humanos , Pulmón/citología , Pulmón/metabolismo , FN-kappa B/genética , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Microaerobic activated sludge (MAS) is a one-stage process operated at 0.5-1.0 mg l-1 dissolved oxygen (DO) aiming at simultaneous nitrification and denitrification. We used molecular techniques and a comprehensive nitrogen (N)-transformation activity test to investigate the dominant NH3 -oxidizing and N2 -producing mechanism as well as the dominant ammonia-oxidizing bacteria (AOB) species in sludge samples individually collected from an MAS system and a conventional anoxic/oxic (A/O) system; both systems were operated at a normal loading rate (i.e. 1.0 kg chemical oxygen demand (COD) m-3 day-1 and 0.1 kg NH4 + -N m-3 day-1 ) in our previous studies. The DO levels in both systems (aerobic: conventional A/O system; microaerobic: MAS system) did not affect the dominant NH3 -oxidizing mechanism or the dominant AOB species. This study further demonstrated the feasibility of a higher loading rate (i.e. 2.30 kg COD m-3 day-1 and 0.34 kg NH4 + -N m-3 day-1 ) with the MAS process during sewage treatment, which achieved a 40% reduction in aeration energy consumption than that obtained in the conventional A/O system. The increase in loading rates in the MAS system did not affect the dominant NH3 -oxidizing mechanism but did impact the dominant AOB species. Besides, N2 was predominantly produced by microaerobic denitrification in the MAS system at the two loading rates.