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1.
Brief Bioinform ; 24(2)2023 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-36892155

RESUMO

Drug-target interaction (DTI) prediction can identify novel ligands for specific protein targets, and facilitate the rapid screening of effective new drug candidates to speed up the drug discovery process. However, the current methods are not sensitive enough to complex topological structures, and complicated relations between multiple node types are not fully captured yet. To address the above challenges, we construct a metapath-based heterogeneous bioinformatics network, and then propose a DTI prediction method with metapath-based hierarchical transformer and attention network for drug-target interaction prediction (MHTAN-DTI), applying metapath instance-level transformer, single-semantic attention and multi-semantic attention to generate low-dimensional vector representations of drugs and proteins. Metapath instance-level transformer performs internal aggregation on the metapath instances, and models global context information to capture long-range dependencies. Single-semantic attention learns the semantics of a certain metapath type, introduces the central node weight and assigns different weights to different metapath instances to obtain the semantic-specific node embedding. Multi-semantic attention captures the importance of different metapath types and performs weighted fusion to attain the final node embedding. The hierarchical transformer and attention network weakens the influence of noise data on the DTI prediction results, and enhances the robustness and generalization ability of MHTAN-DTI. Compared with the state-of-the-art DTI prediction methods, MHTAN-DTI achieves significant performance improvements. In addition, we also conduct sufficient ablation studies and visualize the experimental results. All the results demonstrate that MHTAN-DTI can offer a powerful and interpretable tool for integrating heterogeneous information to predict DTIs and provide new insights into drug discovery.


Assuntos
Desenvolvimento de Medicamentos , Descoberta de Drogas , Simulação por Computador , Descoberta de Drogas/métodos , Proteínas/química , Aprendizagem
2.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37742052

RESUMO

Drug-drug interaction (DDI) prediction can discover potential risks of drug combinations in advance by detecting drug pairs that are likely to interact with each other, sparking an increasing demand for computational methods of DDI prediction. However, existing computational DDI methods mostly rely on the single-view paradigm, failing to handle the complex features and intricate patterns of DDIs due to the limited expressiveness of the single view. To this end, we propose a Hierarchical Triple-view Contrastive Learning framework for Drug-Drug Interaction prediction (HTCL-DDI), leveraging the molecular, structural and semantic views to model the complicated information involved in DDI prediction. To aggregate the intra-molecular compositional and structural information, we present a dual attention-aware network in the molecular view. Based on the molecular view, to further capture inter-molecular information, we utilize the one-hop neighboring information and high-order semantic relations in the structural view and semantic view, respectively. Then, we introduce contrastive learning to enhance drug representation learning from multifaceted aspects and improve the robustness of HTCL-DDI. Finally, we conduct extensive experiments on three real-world datasets. All the experimental results show the significant improvement of HTCL-DDI over the state-of-the-art methods, which also demonstrates that HTCL-DDI opens new avenues for ensuring medication safety and identifying synergistic drug combinations.


Assuntos
Aprendizado Profundo , Interações Medicamentosas , Semântica
3.
Soft Matter ; 19(13): 2350-2359, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36880312

RESUMO

A myriad of natural surfaces such as plant leaves and insect wings can repel water and remain unwetted inspiring scientists and engineers to develop water-repellent surfaces for various applications. Those natural and artificial water-repellent surfaces are typically opaque, containing micro- and nano-roughness, and their wetting properties are determined by the details at the actual liquid-solid interface. However, a generally applicable way to directly observe moving contact lines on opaque water-repellent surfaces is missing. Here, we show that the advancing and receding contact lines and corresponding contact area on micro- and nano-rough water-repellent surfaces can be readily and reproducibly quantified using a transparent droplet probe. Combined with a conventional optical microscope, we quantify the progression of the apparent contact area and apparent contact line irregularity in different types of superhydrophobic silicon nanograss surfaces. Contact angles near 180° can be determined with an uncertainty as low as 0.2°, that a conventional contact angle goniometer cannot distinguish. We also identify the pinning/depinning sequences of a pillared model surface with excellent repeatability and quantify the progression of the apparent contact interface and contact angle of natural plant leaves with irregular surface topography.

4.
BMC Med Educ ; 22(1): 540, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831867

RESUMO

BACKGROUND: The current global pandemic has caused unprecedented strain on critical care resources, creating an urgency for global critical care education programs. Learning needs assessment is a core element of designing effective, targeted educational interventions. In theory, multimodal methods are preferred to assess both perceived and unperceived learning needs in diverse, interprofessional groups, but a robust design has rarely been reported. Little is known about the best approach to determine the learning needs of international critical care professionals. METHOD: We conducted multimodal learning needs assessment in a pilot group of critical care professionals in China using combined quantitative and qualitative methods. The assessments consisted of three phases: 1) Twenty statements describing essential entrustable professional activities (EPAs) were generated by a panel of critical care education experts using a Delphi method. 2) Eleven Chinese critical care professionals participating in a planned education program were asked to rank-order the statements according to their perceived learning priority using Q methodology. By-person factor analysis was used to study the typology of the opinions, and post-ranking focus group interviews were employed to qualitatively explore participants' reasoning of their rankings. 3) To identify additional unperceived learning needs, daily practice habits were audited using information from medical and nursing records for 3 months. RESULTS: Factor analysis of the rank-ordered statements revealed three learning need patterns with consensual and divergent opinions. All participants expressed significant interest in further education on organ support and disease management, moderate interest in quality improvement topics, and relatively low interest in communication skills. Interest in learning procedure/resuscitation skills varied. The chart audit revealed suboptimal adherence to several evidence-based practices and under-perceived practice gaps in patient-centered communication, daily assessment of antimicrobial therapy discontinuation, spontaneous breathing trial, and device discontinuation. CONCLUSIONS: We described an effective mixed-methods assessment to determine the learning needs of an international, interprofessional critical care team. The Q survey and focus group interviews prioritized and categorized perceived learning needs. The chart audit identified additional practice gaps that were not identified by the learners. Multimodal methods can be employed in cross-cultural scenarios to customize and better target medical education curricula.


Assuntos
Educação Médica , Cuidados Críticos , Currículo , Educação Médica/métodos , Humanos , Aprendizagem , Avaliação das Necessidades
5.
Foodborne Pathog Dis ; 18(8): 590-598, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33902323

RESUMO

The China National Center for Food Safety Risk Assessment (CFSA) uses the Foodborne Disease Monitoring and Reporting System (FDMRS) to monitor outbreaks of foodborne diseases across the country. However, there are problems of underreporting or erroneous reporting in FDMRS, which significantly increase the cost of related epidemic investigations. To solve this problem, we designed a model to identify suspected outbreaks from the data generated by the FDMRS of CFSA. In this study, machine learning models were used to fit the data. The recall rate and F1-score were used as evaluation metrics to compare the classification performance of each model. Feature importance and pathogenic factors were identified and analyzed using tree-based and gradient boosting models. Three real foodborne disease outbreaks were then used to evaluate the best performing model. Furthermore, the SHapley Additive exPlanation value was used to identify the effect of features. Among all machine learning classification models, the eXtreme Gradient Boosting (XGBoost) model achieved the best performance, with the highest recall rate and F1-score of 0.9699 and 0.9582, respectively. In terms of model validation, the model provides a correct judgment of real outbreaks. In the feature importance analysis with the XGBoost model, the health status of the other people with the same exposure has the highest weight, reaching 0.65. The machine learning model built in this study exhibits high accuracy in recognizing foodborne disease outbreaks, thus reducing the manual burden for medical staff. The model helped us identify the confounding factors of foodborne disease outbreaks. Attention should be paid not only to the health status of those with the same exposure but also to the similarity of the cases in time and space.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Doenças Transmitidas por Alimentos/epidemiologia , Análise de Perigos e Pontos Críticos de Controle/métodos , Aprendizado de Máquina , Vigilância da População/métodos , China/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Medição de Risco/métodos
6.
Biomed Chromatogr ; 34(3): e4768, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31821576

RESUMO

A highly sensitive, specific and simple LC-MS/MS method for quantification of capmatinib (INC280) in rat plasma was presented. The LC-MS/MS method was validated in terms of specificity and selectivity, linearity, accuracy and precision, matrix effect, extraction recovery, dilution integrity, carryover and stability as per the US Food and Drug Administration's bioanalytical method validation guideline. The validated assay was applied for quantification of capmatinib from a pharmacokinetic study in rats following oral administration at the doses of 1.0, 3.0 and 9.0 mg/kg. The calibration curve ranges from 1 to 2000 ng/ml with desirable linearity and r2 > 0.99. The intra- and inter-batch accuracies were within 99.24-103.59 and 97.76-102.83% with coefficients of variation 5.08-7.36 and 3.18-4.99%, respectively. No significant interference was observed by endogenous peak at the retention time of capmatinib and IS. The assay was free from any matrix effect and showed precise recovery across the calibration curve range, and samples were stable under all experimental conditions. The validated assay was successfully applied to analyze plasma samples of pharmacokinetic study in rat to determine the concentration of capmatinib. In summary, a novel method for analyzing capmatinib in rat plasma has been successfully validated and is now being utilized for quantification of capmatinib from pre-clinical studies.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Imidazóis/sangue , Espectrometria de Massas em Tandem/métodos , Triazinas/sangue , Administração Oral , Animais , Benzamidas , Imidazóis/administração & dosagem , Imidazóis/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Triazinas/administração & dosagem , Triazinas/farmacocinética
7.
Genet Mol Biol ; 43(4): e20200009, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33211058

RESUMO

The purpose of this study was to investigate the expression and clinical value of microRNA-451a (miR-451a) in septic patients and analyze its effect on sepsis-associated cardiac dysfunction and inflammation response. A rat model of sepsis was constructed by cecal ligation and puncture. The expression of miR-451a was measured by quantitative real-time PCR. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of serum miR-451a. The cardiac function and inflammatory responses in septic rats were measured to explore the functional role of miR-451a. Serum expression of miR-451a was increased in septic patients compared with healthy controls, and had the ability to distinguish septic patients from healthy volunteers with a sensitivity and specificity of 87.8% and 81.5%, respectively. Elevated serum miR-451a was associated with sepsis severity, as evidenced by the increased expression of miR-451a in septic shock patients and its correlation with key clinical indicators. Significantly upregulated expression of miR-451a was found in septic patients with cardiac dysfunction, and the knockdown of miR-451a in sepsis rats improved cardiac function and inhibited inflammatory responses. All the data revealed that serum miR-451a serves as a candidate diagnostic biomarker of sepsis and a potential parameter to indicate disease severity. The reduction of miR-451a may mitigate sepsis-induced cardiac dysfunction and inflammatory responses.

8.
Med Sci Monit ; 25: 5986-5991, 2019 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-31401645

RESUMO

BACKGROUND Sepsis is a devastating medical condition. In the USA, about 745 000 people are diagnosed with sepsis annually. Although many anti-inflammatory drugs have been used to manage sepsis, the treatment success rate is very low. This study was undertaken to examine the protective effects of naringenin on sepsis-induced kidney injury in rats. MATERIAL AND METHODS Sepsis was induced in Wistar albino rats by cecal ligation and puncture methods. Histological analysis was performed with hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels were determined by flow cytometery. TUNEL assay was used to demonstrate apoptosis. Sandwich ELISA method was used for the determination of urinary angiotensinogen, and protein expression was determined by Western blot analysis. RESULTS We found that naringenin decreased atrophy in the glomerulus and enabled maintenance of the capsule area and normal tubular cavity of the septic rats. Admistration of naringenin at the dosage of 10 and 20 mg/kg to sepsis rats caused significant reduction in the sepsis-induced apoptosis of kidney cells, accompanied by decrease in Bax and increase in Bcl-2 expression. Moreover, naringenin also decreased the ROS levels in septic rats and downregulated the expression of SOD, CAT, and APX. The effects of naringenin were also examined on the levels of urinary angiotensinogen in sepsis rats. We found that naringenin caused a significant decrease in urinary angiotensinogen levels of septic rats. CONCLUSIONS Naringenin appears to have potential in the treatment of sepsis.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Flavanonas/farmacologia , Sepse/tratamento farmacológico , Angiotensinogênio/urina , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Ceco/patologia , Modelos Animais de Doenças , Rim/patologia , Glomérulos Renais/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Sepse/complicações , Sistema Urinário/patologia
9.
Med Sci Monit ; 25: 5795-5800, 2019 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-31377749

RESUMO

BACKGROUND Sepsis is a severe medical condition. Approximately 0.75 million people are diagnosed with sepsis in the USA annually. Several of anti-inflammatory drugs are used to manage sepsis, but with a very low success rate. This study examined the possible protective effects of a naturally occurring flavanone, quercetin, in a rat model of sepsis. MATERIAL AND METHODS The study was carried out using Wistar albino rats. Sepsis was induced by cecal ligation and puncture methods. Histological analysis was performed by hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels were determined by flow cytometery. Superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) activities were determined by standard assays. Protein expression was determined by Western blot analysis. RESULTS The results showed that quercetin reduced the tissue edema, congestion, and hemorrhage, increased the alveolar volume, and helped to maintain the lung anatomy of septic rats. Admistration of quercetin at the dosage of 15 and 20 mg/kg to septic rats caused significant reduction in the ROS levels. The activities and the expression of SOD, CAT, and APX were significantly decreased upon administration of quercetin in the septic rats at the dosage of 15 and 20 mg/kg. The effects of quercetin were also examined on the expression of the High mobility group box 1 (HMGB1) protein in septic rats. The results showed that quercetin caused a significant decrease in HMGB1 protein levels. CONCLUSIONS The findings of this study suggest that quercetin has therapeutic potential in the treatment of sepsis.


Assuntos
Quercetina/uso terapêutico , Sepse/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Modelos Animais de Doenças , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Proteína HMGB1/metabolismo , Masculino , Quercetina/metabolismo , Quercetina/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Sepse/fisiopatologia , Superóxido Dismutase/metabolismo
11.
Molecules ; 23(11)2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30463372

RESUMO

MOTIVATION: Extensive efforts have been devoted to understanding the antigenic peptides binding to MHC class I and II molecules since they play a fundamental role in controlling immune responses and due their involvement in vaccination, transplantation, and autoimmunity. The genes coding for the MHC molecules are highly polymorphic, and it is difficult to build computational models for MHC molecules with few know binders. On the other hand, previous studies demonstrated that some MHC molecules share overlapping peptide binding repertoires and attempted to group them into supertypes. Herein, we present a framework of the utility of supertype clustering to gain more information about the data to improve the prediction accuracy of class II MHC-peptide binding. RESULTS: We developed a new method, called superMHC, for class II MHC-peptide binding prediction, including three MHC isotypes of HLA-DR, HLA-DP, and HLA-DQ, by using supertype clustering in conjunction with RLS regression. The supertypes were identified by using a novel repertoire dissimilarity index to quantify the difference in MHC binding specificities. The superMHC method achieves the state-of-the-art performance and is demonstrated to predict binding affinities to a series of MHC molecules with few binders accurately. These results have implications for understanding receptor-ligand interactions involved in MHC-peptide binding.


Assuntos
Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe II/metabolismo , Peptídeos/metabolismo , Sítios de Ligação , Análise por Conglomerados , Biologia Computacional/métodos , Antígenos HLA-DP/química , Antígenos HLA-DP/metabolismo , Antígenos HLA-DQ/química , Antígenos HLA-DQ/metabolismo , Antígenos HLA-DR/química , Antígenos HLA-DR/metabolismo , Ligação Proteica
12.
Molecules ; 23(3)2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29495575

RESUMO

RNA-protein interactions (RPIs) have critical roles in numerous fundamental biological processes, such as post-transcriptional gene regulation, viral assembly, cellular defence and protein synthesis. As the number of available RNA-protein binding experimental data has increased rapidly due to high-throughput sequencing methods, it is now possible to measure and understand RNA-protein interactions by computational methods. In this study, we integrate a sequence-based derived kernel with regularized least squares to perform prediction. The derived kernel exploits the contextual information around an amino acid or a nucleic acid as well as the repetitive conserved motif information. We propose a novel machine learning method, called RPiRLS to predict the interaction between any RNA and protein of known sequences. For the RPiRLS classifier, each protein sequence comprises up to 20 diverse amino acids but for the RPiRLS-7G classifier, each protein sequence is represented by using 7-letter reduced alphabets based on their physiochemical properties. We evaluated both methods on a number of benchmark data sets and compared their performances with two newly developed and state-of-the-art methods, RPI-Pred and IPMiner. On the non-redundant benchmark test sets extracted from the PRIDB, the RPiRLS method outperformed RPI-Pred and IPMiner in terms of accuracy, specificity and sensitivity. Further, RPiRLS achieved an accuracy of 92% on the prediction of lncRNA-protein interactions. The proposed method can also be extended to construct RNA-protein interaction networks. The RPiRLS web server is freely available at http://bmc.med.stu.edu.cn/RPiRLS.


Assuntos
Biologia Computacional/métodos , Proteínas de Ligação a RNA/química , RNA/química , Software , Algoritmos , Sequência de Aminoácidos , Área Sob a Curva , Bases de Dados Genéticas , Ligação Proteica , Reprodutibilidade dos Testes , Fluxo de Trabalho
13.
J Assist Reprod Genet ; 32(3): 461-70, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25561158

RESUMO

PURPOSE: To investigate the expression of GRIM-19 (Gene associated with retinoid-interferon-induced mortality 19) in mouse oocytes and preimplantation embryos, and to study the effect of GRIM-19 on the developmental competence of mouse oocytes and embryos. METHODS: GRIM-19 was evaluated at both mRNA and protein levels. The expression of GRIM-19 gene was downregulated in mouse oocytes cultured in vitro by specific small interfering RNA (siRNA) injection, while the activity of GRIM-19 was decreased by microinjection of a GRIM-19 antibody into the cytoplasm of germinal vesicle (GV) oocytes. Oocytes matured in vitro were then fertilized by intracytoplasmic sperm injection (ICSI), followed by observation and evaluation of fertilization rate, cleavage rate, blastocyst formation rate and implantation rate. RESULTS: GRIM-19 is expressed throughout oocyte maturation and preimplantation embryo development stages. GRIM-19 was localized primarily in the cytoplasm of all cells examined. Downregulation of gene expression and activity of GRIM-19 resulted in decreased oocyte viability, potency of oocyte maturation, embryo development and implantation. CONCLUSIONS: GRIM-19 may play important roles in mouse oogenesis and early embryonic development and implantation.


Assuntos
Implantação do Embrião/genética , Desenvolvimento Embrionário/genética , NADH NADPH Oxirredutases/biossíntese , Oócitos/crescimento & desenvolvimento , Oogênese/genética , Animais , Feminino , Fertilização , Fertilização in vitro , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Técnicas de Maturação in Vitro de Oócitos , Masculino , Camundongos , NADH NADPH Oxirredutases/genética , Oócitos/metabolismo , Gravidez
14.
Zhong Yao Cai ; 37(4): 548-52, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-25345121

RESUMO

OBJECTIVE: To break the hard testa and improve seed germination situation of Astragalus membranaceus var. mongholicus, in order to solve the problems of low success rate of seed germination and seedling. METHODS: Longxi Astragalus membranaceus var. mongholicus seed was treated by soaking seed with 75% alcohol and concentrated sulfuric acid, warm-water incubating, grinding and comprehensive treating with warm-water incubating, grinding and sand culture. Its seed germination situation was evaluated by germination potential, germination rate and germination index. RESULTS: Different processing methods significantly improved seed germination with different effect. Comprehensive treatment with warm-water incubating, grinding and sand culture was the best one on Astragalus membranaceus var. mongholicus seed germination. Its germination potential, germination rate and germination index was 66.04%, 87.70% and 1.34,respectively. CONCLUSION: Comprehensive treatment with warm-water incubating, grinding and sand culture is an economic and effective processing method, which is suitable for actual production.


Assuntos
Astragalus propinquus/crescimento & desenvolvimento , Germinação/fisiologia , Plantas Medicinais/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Álcoois/farmacologia , Astragalus propinquus/efeitos dos fármacos , Astragalus propinquus/fisiologia , Germinação/efeitos dos fármacos , Plantas Medicinais/efeitos dos fármacos , Plantas Medicinais/fisiologia , Sementes/efeitos dos fármacos , Sementes/fisiologia , Ácidos Sulfúricos/farmacologia , Temperatura , Fatores de Tempo , Água
15.
Sci Data ; 11(1): 347, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582751

RESUMO

CO2 electroreduction has garnered significant attention from both the academic and industrial communities. Extracting crucial information related to catalysts from domain literature can help scientists find new and effective electrocatalysts. Herein, we used various advanced machine learning, natural language processing techniques and large language models (LLMs) approaches to extract relevant information about the CO2 electrocatalytic reduction process from scientific literature. By applying the extraction pipeline, we present an open-source corpus for electrocatalytic CO2 reduction. The database contains two types of corpus: (1) the benchmark corpus, which is a collection of 6,985 records extracted from 1,081 publications by catalysis postgraduates; and (2) the extended corpus, which consists of content extracted from 5,941 documents using traditional NLP techniques and LLMs techniques. The Extended Corpus I and II contain 77,016 and 30,283 records, respectively. Furthermore, several domain literature fine-tuned LLMs were developed. Overall, this work will contribute to the exploration of new and effective electrocatalysts by leveraging information from domain literature using cutting-edge computer techniques.

16.
Heliyon ; 10(4): e25695, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390092

RESUMO

BACKGROUND: In the process of international communication in Chinese Wushu (ICCW), the government controls the orientation, scale, pace. However, the ICCW currently lacks a standardised government capacity structural system, and a detailed study of framework construction may be required to ensure the smooth development of the ICCW. OBJECTIVES: This study aims to clarify these elements and construct a framework for a governmental capacity system for ICCW. METHODS: For this purpose, an expert interview outline was designed, and in-depth interviews were conducted with 61 experts. Using grounded theory in the qualitative research method, NVivo 12 software was used to conduct a three-level coding analysis of the interview text for data processing and analysis. RESULTS: We extracted 58 opening codes and 11 tree nodes and categorised them into three core categories: supply side government capacity, environment-side government capacity, and demand-side government capacity, accounting for 62.36 %, 24.76 %, and 12.86 % of the total, respectively, which jointly constructed the framework structure system of the governmental capacity system for the ICCW. CONCLUSIONS: This study found that these three-dimensional government capacities have synergistic effects and that multiple measures work together. The government should ensure the supply side's direct promotion effect; the environmental side's indirect influencing effect; and the demand side's internal driving effect to promote ICCW. Meanwhile, a closed-loop systematic study of communication processes should be conducted in combination with communication organisations and individuals.

17.
Heliyon ; 10(6): e27690, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533037

RESUMO

Background: Previous studies have revealed dexmedetomidine have potential protective effects on vital organs by inhibiting the release of inflammatory cytokines. To investigate the effects of dexmedetomidine on sepsis, especially in the initial inflammatory stage of sepsis. RAW264.7 cells were used as the cell model in this study to elucidate the underlying mechanisms. Methods: In this study, we conducted several assays to investigate the mechanisms of dexmedetomidine and HOTAIR in sepsis. Cell viability was assessed using the CCK-8 kit, while inflammation responses were measured using ELISA for IL-1ß, IL-6, and TNF-α. Additionally, we employed qPCR, MeRIP, and RIP to further explore the underlying mechanisms. Results: Our findings indicate that dexmedetomidine treatment enhanced cell viability and reduced the production of inflammatory cytokines in LPS-treated RAW264.7 cells. Furthermore, we observed that the expression of HOTAIR was increased in LPS-treated RAW264.7 cells, which was then decreased upon dexmedetomidine pre-treatment. Further investigation demonstrated that HOTAIR could counteract the beneficial effects of dexmedetomidine on cell viability and cytokine production. Interestingly, we discovered that YTHDF1 targeted HOTAIR and was upregulated in LPS-treated RAW264.7 cells, but reduced in dexmedetomidine treatment. We also found that YTHDF1 increased HOTAIR and HOTAIR m6A levels. Conclusions: Collectively, our results suggest that dexmedetomidine downregulates HOTAIR and YTHDF1 expression, which in turn inhibits the biological behavior of LPS-treated RAW264.7 cells. This finding has potential implications for the prevention and treatment of sepsis-induced kidney injury.

18.
Lab Chip ; 24(6): 1586-1601, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38362645

RESUMO

The rapid advancement in the fabrication and culture of in vitro organs has marked a new era in biomedical research. While strides have been made in creating structurally diverse bioartificial organs, such as the liver, which serves as the focal organ in our study, the field lacks a uniform approach for the predictive assessment of liver function. Our research bridges this gap with the introduction of a novel, machine-learning-based "3P model" framework. This model draws on a decade of experimental data across diverse culture platform studies, aiming to identify critical fabrication parameters affecting liver function, particularly in terms of albumin and urea secretion. Through meticulous statistical analysis, we evaluated the functional sustainability of the in vitro liver models. Despite the diversity of research methodologies and the consequent scarcity of standardized data, our regression model effectively captures the patterns observed in experimental findings. The insights gleaned from our study shed light on optimizing culture conditions and advance the evaluation of the functional maintenance capacity of bioartificial livers. This sets a precedent for future functional evaluations of bioartificial organs using machine learning.


Assuntos
Órgãos Bioartificiais , Fígado Artificial , Fígado , Albuminas
19.
BMC Genomics ; 14 Suppl 2: S2, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23445458

RESUMO

BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation in human DNA. The sequence of SNPs in each of the two copies of a given chromosome in a diploid organism is referred to as a haplotype. Haplotype information has many applications such as gene disease diagnoses, drug design, etc. The haplotype assembly problem is defined as follows: Given a set of fragments sequenced from the two copies of a chromosome of a single individual, and their locations in the chromosome, which can be pre-determined by aligning the fragments to a reference DNA sequence, the goal here is to reconstruct two haplotypes (h1, h2) from the input fragments. Existing algorithms do not work well when the error rate of fragments is high. Here we design an algorithm that can give accurate solutions, even if the error rate of fragments is high. RESULTS: We first give a dynamic programming algorithm that can give exact solutions to the haplotype assembly problem. The time complexity of the algorithm is O(n × 2t × t), where n is the number of SNPs, and t is the maximum coverage of a SNP site. The algorithm is slow when t is large. To solve the problem when t is large, we further propose a heuristic algorithm on the basis of the dynamic programming algorithm. Experiments show that our heuristic algorithm can give very accurate solutions. CONCLUSIONS: We have tested our algorithm on a set of benchmark datasets. Experiments show that our algorithm can give very accurate solutions. It outperforms most of the existing programs when the error rate of the input fragments is high.


Assuntos
Algoritmos , Biologia Computacional/métodos , Haplótipos , Análise de Sequência de DNA/métodos , DNA/genética , Humanos , Polimorfismo de Nucleotídeo Único
20.
Turk J Anaesthesiol Reanim ; 51(5): 408-413, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37876167

RESUMO

Objective: The prognostic utility of inflammatory markers in survival has been suggested in patients with cancer; however, evidence on their prognostic value in severely ill patients is very limited. We aimed to explore the prognostic value of cholinesterase (ChE), C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) in predicting mortality in patients from the intensive care unit (ICU). Methods: Serum levels of ChE, CRP, IL-6 and PCT were measured in ICU patients from December 13th, 2019 to June 28th, 2022. We assessed the predictive power of ChE, CRP, IL-6, and PCT using the receiver operating characteristic (ROC) curves. Furthermore, we evaluated their diagnostic accuracy by comparing the areas under the ROC curve (AUCs) along with their corresponding 95% confidence intervals (CIs). The cut-off values were determined to dichotomise these biomarkers, which were then included in multivariable logistic regression models to examine their relationship with ICU mortality. Results: Among 253 ICU patients included in the study, 66 (26%) died during the ICU stay. The AUCs to predict ICU mortality were 0.643 (95% CI, 0.566-0.719), 0.648 (95% CI, 0.633-0.735), 0.643 (95% CI, 0.563-0.723) and 0.735 (95% CI, 0.664-0.807) for ChE, CRP, IL-6 and PCT, respectively. After adjusting for age, sex and disease severity, lower ChE level (<3.668 × 103 U L-1) and higher levels of CRP (>10.546 mg dL-1), IL-6 (>986.245 pg mL-1) and PCT (>0.505 µg L-1) were associated with higher mortality risk, with odd ratios of 2.70 (95% CI, 1.32-5.54), 4.99 (95% CI, 2.41-10.38), 3.24 (95% CI, 1.54-6.78) and 3.67 (95% CI, 1.45-9.95), respectively. Conclusion: ChE, CRP, IL-6 and PCT were independent ICU mortality risk factors in severely ill patients. Elevated PCT levels exhibited better predictive value than the other three biomarkers that were evaluated.

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