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1.
bioRxiv ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38645053

RESUMO

In the last decade cellular senescence, a hallmark of aging, has come into focus for pharmacologically targeting aging processes. Senolytics are one of these interventive strategies that have advanced into clinical trials, creating an unmet need for minimally invasive biomarkers of senescent cell load to identify patients at need for senotherapy. We created a landscape of miRNA and mRNA expression in five human cell types induced to senescence in-vitro and provide proof-of-principle evidence that miRNA expression can track senescence burden dynamically in-vivo using transgenic p21 high senescent cell clearance in HFD fed mice. Finally, we profiled miRNA expression in seven different tissues, total plasma, and plasma derived EVs of young and 25 months old mice. In a systematic analysis, we identified 22 candidate senomiRs with potential to serve as circulating biomarkers of senescence not only in rodents, but also in upcoming human clinical senolytic trials.

2.
Cancers (Basel) ; 16(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38473331

RESUMO

Obesity is strongly associated with occurrence, metastasis, and resistance to therapy in breast cancers, which also exhibit high adipose content in the tumor microenvironment. Adipose tissue-derived mesenchymal stromal cells (ASCs) are recruited to breast cancer by many mechanisms, including hypoxia, and contribute to metastatic transition of the cancer. Breast cancers are characterized by regions of hypoxia, which can be temporally unstable owing to a mismatch between oxygen supply and consumption. Using a high-sensitivity nanopatterned stromal invasion assay, we found that ASCs could promote stromal invasion of not only breast cancer cell lines but also MCF10A1, a cell line derived from untransformed breast epithelium. RNA sequencing of MCF10A1 cells conditioned with medium from ASCs revealed upregulation of genes associated with increased cell migration, chemotaxis, and metastasis. Furthermore, we found that fluctuating or oscillating hypoxia could induce senescence in ASCs, which could result in an increased invasive potential in the treated MCF10A1 cells. These findings highlight the complex interplay within the breast cancer microenvironment, hypoxia, and the role of ASCs in transforming even non-cancerous breast epithelium toward an invasive phenotype, providing insights into early metastatic events.

3.
Sci Rep ; 14(1): 5658, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454072

RESUMO

In vivo cardiac diffusion tensor imaging (cDTI) is a promising Magnetic Resonance Imaging (MRI) technique for evaluating the microstructure of myocardial tissue in living hearts, providing insights into cardiac function and enabling the development of innovative therapeutic strategies. However, the integration of cDTI into routine clinical practice poses challenging due to the technical obstacles involved in the acquisition, such as low signal-to-noise ratio and prolonged scanning times. In this study, we investigated and implemented three different types of deep learning-based MRI reconstruction models for cDTI reconstruction. We evaluated the performance of these models based on the reconstruction quality assessment, the diffusion tensor parameter assessment as well as the computational cost assessment. Our results indicate that the models discussed in this study can be applied for clinical use at an acceleration factor (AF) of × 2 and × 4 , with the D5C5 model showing superior fidelity for reconstruction and the SwinMR model providing higher perceptual scores. There is no statistical difference from the reference for all diffusion tensor parameters at AF × 2 or most DT parameters at AF × 4 , and the quality of most diffusion tensor parameter maps is visually acceptable. SwinMR is recommended as the optimal approach for reconstruction at AF × 2 and AF × 4 . However, we believe that the models discussed in this study are not yet ready for clinical use at a higher AF. At AF × 8 , the performance of all models discussed remains limited, with only half of the diffusion tensor parameters being recovered to a level with no statistical difference from the reference. Some diffusion tensor parameter maps even provide wrong and misleading information.


Assuntos
Aprendizado Profundo , Imagem de Tensor de Difusão , Imagem de Tensor de Difusão/métodos , Algoritmos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Imagem de Difusão por Ressonância Magnética/métodos
4.
ACS Nano ; 18(5): 4038-4055, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38270088

RESUMO

Diagnosis of benign and malignant small nodules of the lung remains an unmet clinical problem which is leading to serious false positive diagnosis and overtreatment. Here, we developed a serum protein fishing-based spectral library (ProteoFish) for data independent acquisition analysis and a machine learning-boosted protein panel for diagnosis of early Non-Small Cell Lung Cancer (NSCLC) and classification of benign and malignant small nodules. We established an extensive NSCLC protein bank consisting of 297 clinical subjects. After testing 5 feature extraction algorithms and six machine learning models, the Lasso algorithm for a 15-key protein panel selection and Random Forest was chosen for diagnostic classification. Our random forest classifier achieved 91.38% accuracy in benign and malignant small nodule diagnosis, which is superior to the existing clinical assays. By integrating with machine learning, the 15-key protein panel may provide insights to multiplexed protein biomarker fishing from serum for facile cancer screening and tackling the current clinical challenge in prospective diagnostic classification of small nodules of the lung.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Pulmão/patologia , Algoritmos , Aprendizado de Máquina , Proteínas Sanguíneas
5.
Artif Organs ; 48(1): 37-49, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37846614

RESUMO

BACKGROUND: The artificial anal sphincter (AAS) system has gained significant attention as a solution for treating fecal incontinence (FI). It relies on transcutaneous energy transfer (TET) as its primary energy source. However, changes in posture or biological tissue can cause misalignment of the coil, resulting in unstable power reception. Inadequate power affects charging efficiency, while excessive power leads to excessive heating at the receiver side. Consequently, achieving safe and constant voltage charging for the AAS becomes a complex challenge. METHODS: To maintain a consistent charging voltage and overcome the issue of variations in load and coil coupling strength, this article proposes a wireless charging control system that utilizes an LCC-S-type resonant network and phase shift to adjust the transmitting voltage based on feedback charging voltage in real time. In particular, the PI controller and neural network are introduced to change the phase-shift angle swiftly. The dynamic performance is then evaluated under different misalignments and presented with comparative results. RESULTS: The results indicate that the multilayer perceptron control system outperforms the PI. Under the complex misalignment disturbance, the average error of receiver side load voltage is only 0.007 V, with an average settling time of 960 ms. Additionally, the average temperature at the receiver side is 40.4°C. CONCLUSION: The experiments demonstrate that the proposed system effectively addresses the misalignment issue in TET during the charging, ensuring constant voltage charging at the receiver side and thermal safety.


Assuntos
Órgãos Artificiais , Esfíncter Urinário Artificial , Canal Anal/cirurgia , Transferência de Energia , Redes Neurais de Computação
6.
Gels ; 9(12)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38131936

RESUMO

Hydrogel has been widely used in reservoir regulation for enhancing oil recovery, however, this process can experience negative influences on the properties and effects of the hydrogels. Therefore, developing novel hydrogels with excellent environmental responsiveness would improve the formation adaptability of hydrogels. In this study, novel polyvinyl polyamine hydrogels were synthesized by a ring-opening addition reaction between polyvinyl polyamines and polyethylene glycol glycidyl ether. The results of atomic force microscopy and transmission electron microscopy showed that the polyvinyl polyamine gel had a porous and irregular bulk structure and was endowed with water storage. With the temperature rising from 30 °C to 60 °C, the transmittance of diethylenetriamine hydrogel decreased from 84.3% to 18.8%, indicating that a phase transition had occurred. After the polyvinyl polyamine hydrogel with low initial viscosity was injected into the formation in the liquid phase, the increase of the reservoir temperature caused it to turn into an elastomer, thereby migrating to the depth of the reservoir and achieving effective plugging. Polyvinyl polyamine hydrogel could improve the profile of heterogeneous layers significantly by forcing subsequent fluids into the low permeability zone in the form of elastomers in the medium temperature reservoirs of 40-60 °C. The novel environmentally responsive polyvinyl polyamine hydrogels, capable of phase transformation with temperature, exhibited superior performance in recovering residual oil, which was beneficial for applications in reservoir profile control and oilfield development.

7.
BMC Biol ; 21(1): 237, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37904147

RESUMO

BACKGROUND: Melanin plays important roles in morphological development, survival, host-pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. RESULTS: We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. CONCLUSIONS: Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.


Assuntos
Ascomicetos , Verticillium , Melaninas , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Verticillium/genética , Dedos de Zinco , Doenças das Plantas/microbiologia
8.
Artif Organs ; 47(11): 1710-1719, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37680050

RESUMO

BACKGROUND: Artificial anal sphincter is an implantable medical device for treating fecal incontinence. Reasonable simulation facilitates the advancement of research and reduces experiments on biological tissue. However, the device's clamping motion and sensor interaction with the intestine in the simulation still require further exploration. This article presents a simulation of the artificial anal sphincter's clamping and sensing and its interaction with the intestinal environment using the Simulation Open Framework Architecture (SOFA). METHODS: Firstly, the proposed simulation algorithm and its principles in SOFA are analyzed. Secondly, the clamping motion and sensor system of the artificial anal sphincter are simulated. Thirdly, a finite element model of intestine is established based on the properties of intestinal soft tissue. Finally, the in vitro experiments are performed. RESULTS: The simulation results indicate that the sensor system of the artificial anal sphincter has good sensing performance during the clamping motion and fecal accumulation process. Experiments have shown that optimal sensory capabilities can be achieved as the posture of the artificial anal sphincter with a roll angle between 20° and 40°. The comparison demonstrates a mean absolute error of 10%-20% between simulation and in vitro experimental results for sensor forces, which verifies the effectiveness of the simulation. CONCLUSION: The proposed novel simulation achieves a more comprehensive interaction between the artificial anal sphincter motion and intestinal environment. This study may provide more effective simulation data for guidance in improving the performance of sensor perception of artificial anal sphincter for further research.


Assuntos
Órgãos Artificiais , Incontinência Fecal , Esfíncter Urinário Artificial , Humanos , Canal Anal/cirurgia , Próteses e Implantes , Incontinência Fecal/cirurgia
9.
Mater Horiz ; 10(11): 5192-5201, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37725333

RESUMO

Wearable electrochemical sensors have shown potential for personal health monitoring due to their ability to detect biofluids non-invasively at the molecular level. Smart fibers with high flexibility and comfort are currently ideal for fabricating electrochemical sensors, but little research has focused on fluid transport at the human-machine interface, which is of great significance for continuous and stable monitoring and skin comfort. Here, we report an electrochemical sensing fiber with a special core-sheath structure, whose outer layer is wound by nanofibers with a hierarchical Fermat helix structure which has excellent moisture conductivity, and the inner layer is based on CNT fibers covered by three-dimensional reduced graphene oxide folds which have good sensing properties after modification of active materials such as enzymes and selective membranes. This kind of fiber enables efficient sweat capture, and thus only 0.1 µL of sweat is required to activate the device, and it responds very quickly (1.5 s). The fibers were further integrated into a garment to build a wireless sweat detection system, enabling stable monitoring of six physiological markers in sweat (glucose, lactate, Na+, K+, Ca2+, and pH). This work provides a feasible proposal for future personalized medicine and the construction of "smart sensing garments".


Assuntos
Técnicas Biossensoriais , Dispositivos Eletrônicos Vestíveis , Humanos , Técnicas Biossensoriais/métodos , Suor/química , Pele , Biomarcadores/análise
10.
Neuroreport ; 34(13): 655-663, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37506317

RESUMO

This study was designed to see the expression of toll-like receptor 4 (TLR4) and downstream molecules including myeloid differentiation factor 88 (MyD88) and interleukin 1-ß (IL-1ß) in the spinal cord as peripheral nerve injury recovered in mice. We established a model of femoral nerve injury (FNI) in C57BL/6 mice by transection of the motor branch of the femoral nerve, followed by retrograde labeling to show the according motor neurons in the anterior horn of the spinal cord pars lumbar. We observed the motor function recovery of the injured hind limbs using behavioral tests. The expression of TLR4, MyD88, and IL-1ß was examined by immunofluorescent staining and western blot. According to the behavior test, the FNI animals fully recovered within 6-8 weeks. TLR4, MyD88, and IL-1ß were expressed in the ventral horn of the spinal cord both at 72 h till 6 weeks after the femoral nerve transection surgery, and these proteins were mostly co-localized with neurons. IL-1ß also tended to rise in the same surgery groups, but more intimate with microglia surrounding nearby retrograde labeled neurons. And western blot results were consistent with histological findings. The results indicate that peripheral nerve injury may induce innate immune reactions of the central neurons and critical signaling like TLR4/MyD88 in the spinal cord may reflect the recovery of the injury. These findings suggest that peripheral nerve injury triggered the TLR4/MyD88 signal in the soma of spinal neurons may be involved in function and nerve restoration through neuron-glia crosstalk.


Assuntos
Fator 88 de Diferenciação Mieloide , Traumatismos dos Nervos Periféricos , Camundongos , Animais , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Nervo Femoral/metabolismo , Camundongos Endogâmicos C57BL , Neurônios Motores/metabolismo
11.
Ann Clin Transl Neurol ; 10(5): 836-841, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37000961

RESUMO

Infant-type hemispheric glioma, a new subtype of pediatric high-grade glioma, arises in the cerebral hemispheres. Despite better survival outcomes, the treatment of infant-type hemispheric glioma is still facing challenges. Here, we reported a case of QKI-ALK fusion, infant-type hemispheric glioma with lung metastasis who achieved a complete clinical response after lorlatinib treatment. This typical case demonstrated the importance of appropriate molecularly targeted treatments in ALK-fused tumors, and lorlatinib may serve as an effective complement to conventional chemotherapy and radiotherapy in primary glioma harboring ALK fusions and its metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Glioma , Neoplasias Pulmonares , Humanos , Lactente , Criança , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Quinase do Linfoma Anaplásico/uso terapêutico , Inibidores de Proteínas Quinases , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Lactamas Macrocíclicas/uso terapêutico , Glioma/tratamento farmacológico
12.
Eur Spine J ; 32(4): 1326-1333, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36829066

RESUMO

PURPOSE: Clinical outcome of spinal cavernous malformation (SCM) varies because of its unclear natural history, and reliable prognostic prediction model for SCM patients is limited. The aim of the present study was to investigate potential factors that predict one-year neurological status in postoperative patients with SCM. METHODS: This was a multicenter prospective observational study in consecutive patients with SCMs. SCMs treated microsurgically between January 2015 and January 2021 were included. Outcome was defined as the American Spinal Injury Association Impairment Scale (AIS) grade at one year after operation. Multivariable analyses were used to construct the best predictive model for patient outcomes. RESULTS: We identified 268 eligible SCM patients. Neurological outcome had worsened from preoperative baseline in 51 patients (19.0%) at one year. In the multivariable logistic regression, the best predictive model for unfavorable outcome included symptom duration ≥ 26 months (95% CI 2.80-16.96, P < 0.001), size ≤ 5 mm (95% CI 1.43-13.50, P = 0.010), complete intramedullary (95% CI 1.69-8.14, P = 0.001), subarachnoid hemorrhage (95% CI 2.92-12.57, P < 0.001), AIS B (95% CI 1.91-40.93, P = 0.005) and AIS C (95% CI 1.12-14.54, P = 0.033). CONCLUSIONS: Admission size of the lesion, morphology, symptom duration, AIS grade and the presence of subarachnoid hemorrhage were strong outcome predictors regarding prognostication of neurological outcome in postoperative patients with SCMs. A decision to surgically remove a symptomatic SCM should be justified by systematic analysis of all factors potentially affecting outcome.


Assuntos
Anormalidades Musculoesqueléticas , Hemorragia Subaracnóidea , Humanos , Estudos Prospectivos , Procedimentos Neurocirúrgicos , Prognóstico , Resultado do Tratamento , Estudos Retrospectivos
13.
Ann Transl Med ; 10(19): 1069, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36330384

RESUMO

Background: Roxadustat is a newly marketed hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat anemia in patients with end-stage renal disease (ESRD). While clinical trials have demonstrated the therapeutic effects of roxadustat in patients with ESRD who are resistant to erythropoiesis-stimulating agents (ESAs), its metabolic effects are still unclear. Methods: Thirty-two individuals with ESRD and ESA resistance from the Blood Purification Center of Dalian Municipal Central Hospital were included. A total of 96 fasting serum samples were obtained from participants before treatment with roxadustat, and after treatment for 15 and 30 days. Ultra-high performance liquid chromatography-mass spectrometry-based metabolomics and lipidomics strategies were applied to investigate the effects of roxadustat on serum metabolism. Results: A total of 255 metabolites and 444 lipid molecular species were detected and quantified. Sphingolipids and phospholipids decreased significantly during treatment, possibly associated with changes in phospholipid and ceramide metabolism. Bile acid levels decreased and cholic acid/chenodeoxycholic acid increased, indicating changes in gut microbiota and bile acid metabolism. Amino acids also changed during the process of treatment. Conclusions: The present study showed sphingolipids, phospholipids, and bile acids were significantly altered, which may be associated with a changed metabolism caused by roxadustat. This approach provided a powerful tool for exploring the mechanisms of ESA resistance in ESRD patients and may represent a promising strategy for elucidating the complex therapeutic mechanisms of other drugs.

14.
Sensors (Basel) ; 22(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36236504

RESUMO

Monitoring bodily pressure could provide valuable medical information for both doctors and patients. Long-term implantation of in vivo sensors is highly desirable in situations where perception reconstruction is needed. In particular, for fecal incontinence, artificial anal sphincters without perceptions could not remind patients when to defecate and even cause ischemic tissue necrosis due to uncontrolled clamping pressure. To address these issues, a novel self-packaging strain gauge sensor system is designed for in vivo perception reconstruction. In addition, long short-term memory (LSTM) networks, which show excellent performance in processing time series-related features and fitting properties, are used in this article to improve the prediction accuracy of the perception model. The proposed system has been tested and compared with the traditional linear regression (LR) approach using data from in vitro experiments. The results show that the Root-Mean-Square Error (RMSE) is reduced by more than 69%, which demonstrates that the prediction accuracy of the proposed LSTM model is higher than that of the LR model to reach a more accurate prediction of the amount of intestinal content. Furthermore, outcomes of in vivo experiments show that the robustness of the novel sensor system based on long short-term memory networks is verified through experiments with limited data.


Assuntos
Incontinência Fecal , Memória de Curto Prazo , Canal Anal/cirurgia , Incontinência Fecal/cirurgia , Humanos , Memória de Longo Prazo , Percepção
15.
Int J Mol Sci ; 23(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36142710

RESUMO

Pine wilt disease (PWD) is a global quarantine disease of forests that mainly affects Pinaceae species. The disease spreads rapidly. Once infected, pine trees have an extremely high mortality rate. This paper provides a summary of the common techniques used to detect PWD, including morphological-, molecular-, chemical- and physical-based methods. By comprehending the complex relationship among pinewood nematodes, vectors and host pine trees and employing the available approaches for nematode detection, we can improve the implementation of intervention and control measures to effectively reduce the damage caused by PWD. Although conventional techniques allow a reliable diagnosis of the symptomatic phase, the volatile compound detection and remote sensing technology facilitate a rapid diagnosis during asymptomatic stages. Moreover, the remote sensing technology is capable of monitoring PWD over large areas. Therefore, multiple perspective evaluations based on these technologies are crucial for the rapid and effective detection of PWD.


Assuntos
Pinus , Rabditídios , Animais
16.
Artif Organs ; 46(12): 2391-2399, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35866428

RESUMO

BACKGROUND: Artificial organs are playing an increasingly important role in medical field. Artificial anal sphincter, as an example, is a widely used medical device for fecal incontinence. Though it could help patients maintain continence, the issue of perception reconstruction is still unsolved, which means that patients cannot control defecation as desired. METHODS: In this paper, a novel sensor system based on vector similarity has been analyzed and evaluated. The sensor system is a self-packaged strain gauge sensor with a small size 14.5 mm × 6 mm, especially for medical device implanted in body to reconstruct perception function. In order to overcome the disadvantages of single threshold judgment, a more accurate and reliable judgment standard for content pressure detection in rectum is developed by using vector similarity method. Therefore, in the novel sensor system, standard multi-parameters are comprehensive considered. Furthermore, weight-optimization of sensors are investigated since each sensor has played a different role in detection. Finally, sensor calibration, in vitro and in vivo experiments are established. RESULTS: In sensor calibration, the result R2 > 0.99 presents the strain gauge pressure sensor has a good linearity. After that, a series of in vitro experiments have been conducted. The optimized sensor system shows a high accuracy rate in perception reconstruction, which is 87.5% on early warning and 95% on the alarm. In the following in vivo experiments. The results indicate that the average accuracy of the proposed perception reconstruction module has increased by 17.7%, compared with that without optimized sensor system. CONCLUSIONS: All of these have proven that the novel perception reconstruction module with sensor system based on vector similarity is more acceptable and reliable.


Assuntos
Órgãos Artificiais , Incontinência Fecal , Humanos , Canal Anal/cirurgia , Incontinência Fecal/cirurgia , Reto/cirurgia , Percepção
17.
Int J Inj Contr Saf Promot ; 29(4): 463-474, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35666171

RESUMO

Mitigating e-bicycle crash occurrence has become a great challenge across the world. It is of paramount importance for improving traffic safety to characterize the relationship between e-bicycle crash injury severities and contributing factors. This study positions itself at clarifying the roles of the factors in e-bicycle crashes from time, space, road, environment, rider and object characteristics. The partial proportional odds (PPOs) model as well as its elasticity analysis was employed to identify the influences based on 15,138 police-reported e-bicycle crashes in Shangyu District of Shaoxin City, China. The results evidenced that there were 12 factors having significant effects. Especially, the results emphasized the greater influences of rider gender, age, object hit and road type. Their maximum of the absolutes of elasticities was greater than 24%. Increased crash severity was associated with females, younger riders, and higher speed collisions. However, the remaining significant variables had minor effects (no more than 10%). The findings provide meaningful insights for advancing e-bicycle development, when making related policies and prioritizing safety countermeasures.


Assuntos
Acidentes de Trânsito , Polícia , Feminino , Humanos , Ciclismo/lesões , Cidades , China/epidemiologia
18.
Anal Chim Acta ; 1215: 339979, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35680341

RESUMO

Metabolomics-based precision medicine is facing several obstacles including cross-platform data comparison issue and the lack of metabolome benchmark values of healthy population, one of main reasons is the shortage of comprehensive metabolome quantitation methods. Here, we developed an alternate reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) method to quantitatively determine metabolites and lipids. Assisted by a wide set of reference standards and real samples, up to 397 multiple reaction monitoring (MRM) transitions (239 for positive and 158 for negative ion modes) and 1080 MRM transitions (607 for positive and 473 for negative ion modes) were defined respectively in the metabolomic and lipidomic analyses with more than 1000 metabolites and lipids being quantified. Among them, 144 analytes including amines, amino acids, benzenoids, peptides, nucleobases and related, bile acids, carboxylic acids, fatty acids, hormones, indoles and others were absolutely quantified, while carnitines, lyso-phosphatidylcholines, lyso-phosphatidylethanolamines, free fatty acids, sphingomyelins, phosphatidylcholines (PCs), alkyl and alkenyl substituted PCs, phosphatidylethanolamines (PEs), alkyl and alkenyl substituted PEs and triacylglycerols were semiquantified. The developed method was validated to have good analytical characteristics. Analytical results of standard reference material 1950 human plasma had a good agreement with literature data. As a proof of application, this method was used to study serum metabolic pattern changes of patients with hyperuricemia and nonalcoholic fatty liver. This alternate RPLC-MS method for quantitative metabolites and lipids analysis can further be used to provide technology and large-scale data support for precision medicine and life sciences.


Assuntos
Lipidômica , Fosfatidiletanolaminas , Aminas , Humanos , Metaboloma , Metabolômica/métodos , Fosfatidilcolinas
19.
Bioorg Chem ; 125: 105867, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35576739

RESUMO

Baeyer-Villiger monooxygenase (BVMO) mediated sulfoxidation is a sustainable approach for the synthesis of esomeprazole. In this work, a novel phenylacetone monooxygenase from Limnobacter sp. (LnPAMO) was found to have trace activity for synthesis of enantiopure esomeprazole. Through engineering in the substrate tunnel using a mutagenesis strategy called "nonpolarity paving" and some modifications in cofactor binding domains, a mutant harboring 15 mutations (LnPAMO Mu15) was obtained with 6.6 × 103-fold higher activity to convert omeprazole sulfide into esomeprazole. The activities of the mutant for synthesis of (S)-methyl phenyl sulfoxide and (S)-pantoprazole also increased much, indicating the versatility of the mutant for sulfoxide synthesis. Importantly, no over-oxidation byproduct omeprazole sulfone was detected in the sulfoxidation products by both mass spectrometry and HPLC analysis. Then NADP-dependent Burkholderia stabili formate dehydrogenase was ligated behind Mu15 along with a ribosome binding site sequence in pET-28a for co-expression. By single whole-cell of recombinant Escherichia coli BL21 coexpressing Mu15 and formate dehydrogenase, omeprazole sulfide was efficiently converted into esomeprazole without production of sulfone (16 g/L substrate, enantiomeric excess > 99.9% (S) and > 99% conversion) and the space-time-yield reached 1.67 g product/L/h.


Assuntos
Esomeprazol , Oxigenases de Função Mista , Acetona/análogos & derivados , Acetona/metabolismo , Escherichia coli/genética , Esomeprazol/metabolismo , Formiato Desidrogenases/metabolismo , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Oxirredução , Especificidade por Substrato
20.
Small ; 18(15): e2107778, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35257482

RESUMO

Electrochemical (EC) actuators have garnered significant attention in recent years, yet there are still some critical challenges to limit their application range, such as responsive time, multifunctionality, and actuating direction. Herein, an EC actuator with a back-to-back structure is fabricated by stacking two membranes with bilayer V2 O5 nanowires/single-walled carbon nanotubes (V2 O5 NWs/SWCNTs) networks, and shows a synchronous high actuation amplitude (about ±9.7 mm, ±28.4°) and multiple color changes. In this back-to-back structure, the inactive SWCNTs layer is used as a conductive current collector, and the bilayer network is attached to a porous polymer membrane. The dual-responsive processes of V2 O5 nanowires (V2 O5 NWs) actuation films and actuators are also deeply investigated through in situ EC X-ray diffraction and Raman spectroscopy. The results show that the EC actuation of the V2 O5 NWs/SWCNTs film is highly related to the redox behavior of the pseudocapacitive V2 O5 NWs layer. At last, both V2 O5 NWs and W18 O49 nanowires (W18 O49 NWs)-based EC actuators are constructed to demonstrate the multicolor changes and multidirectional actuation induced by the opposite lattice changes of V2 O5 NWs and W18 O49 NWs during ionic de-/intercalation, guiding the design of multifunctional EC actuators in the future.


Assuntos
Nanotubos de Carbono , Nanofios , Íons , Nanotubos de Carbono/química , Nanofios/química , Polímeros/química , Porosidade
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