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1.
J Cancer ; 15(10): 3076-3084, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706905

RESUMO

Background: Glioma represents the predominant subtype of brain tumor, characterized by an unfavorable prognosis. Current evidence indicates the involvement of microRNAs (miRNAs) in the initiation and progression of glioma malignancies. While miR-760 has been recognized in the context of tumorigenesis, its precise role in gliomas remains insufficiently explored. Methods: In this investigation, we harnessed the GSE25631 database to scrutinize the aberrant expression profiles of microRNAs, whereby the diminished expression of miR-760 in glioblastoma was validated. Our aim was to delineate the expression patterns of microRNA-760 (miR-760) and probe its prognostic significance within the realm of glioma. Employing quantitative real-time polymerase chain reaction, we ascertained the relative expression levels of miR-760 and MMP2 in glioma cell lines. The impact of miR-760 on cell proliferation, migration, and invasion was assessed through Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assays. Bioinformatics analysis corroborated the downstream target gene of miR-760. Furthermore, a luciferase reporter experiment was conducted to pinpoint MMP2 as the direct target gene of miR-760. The assessment of MMP2 protein levels was accomplished through Western blotting and immunofluorescence techniques. Result: Our data unequivocally revealed a substantial reduction in miR-760 expression within glioma tissues and cell lines. Heightened miR-760 levels exerted a restraining influence on the proliferation, migration, and invasion capabilities of glioma cell lines. The outcomes of our bioinformatics analysis unveiled the ability of miR-760 to engage with and curtail MMP2 expression. Collectively, these findings posit that miR-760 exerts a restraining influence on glioma growth by orchestrating the upregulation of miR-760 along the miR-760/MMP2 axis. Conclusion: The delineation of the miR-760/MMP2 axis promises to broaden our comprehension of the intricate molecular mechanisms underpinning glioma proliferation and may unveil prospective therapeutic avenues for the management of glioma.

2.
Development ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646855

RESUMO

Ecdysone-induced protein 93 (E93), known as the "adult-specifier" transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. While E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discovered that in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNAs are broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we revealed that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.

3.
Sci Rep ; 14(1): 9800, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684705

RESUMO

With the rapid advancement of urbanization and industrialization, ecological patches within cities and towns are fragmented and ecological corridors are cut off, regional ecological security is threatened and sustainable development is hindered. Building an ecological network that conforms to regional realities can connect fragmented patches, protect biodiversity and regional characteristics, and provide scientific reference for regional ecological protection and ecological network planning. By taking Qilin District, the main urban area of Qujing City as an example, and using geospatial data as the main data source, based on morphological spatial pattern analysis (MSPA) and minimum cumulative resistance (MCR), this study identified ecological source areas, extracted ecological corridors, and build & optimize ecological networks. (1) All landscape types are identified based on MSPA, the proportion of core area was the highest among all landscape types, which was 80.69%, combined with the connectivity evaluation, 14 important ecological source areas were selected. (2) 91 potential ecological corridors were extracted through MCR and gravity models, there were 16 important ones. (3) The network connectivity analysis method is used to calculate the α, ß, and γ indexes of the ecological network before optimization, which were 2.36, 6.5, and 2.53, while after optimization, α, ß and γ indices were 3.8, 9.5 and 3.5, respectively. The combined application of MSPA-MCR model and ecological network connectivity analysis evaluation is conducive to improving the structure and functionality of ecological network.

4.
Clin Respir J ; 18(5): e13749, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685745

RESUMO

BACKGROUND AND OBJECTIVE: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were significant and succinct indicators of systemic inflammation. We assessed the influence of stereotactic body radiotherapy (SBRT) on NLR and PLR in patients with locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: We reviewed the medical data of patients with LA-NSCLC who underwent SBRT between 1 January 2013 and 31 December 2018. NLR and PLR values recorded at pre- and post-SBRT were examined. We assessed the correlation between pre/post-SBRT NLR and PLR and survival outcomes. The decision tree evaluation was conducted using Chi-square automatic detection. RESULTS: In total, 213 patients were included in the study with a median follow-up duration of 40.00 (ranging from 5.28 to 100.70) months. Upon dichotomization by a median, we identified that post-SBRT NLR > 5.5 and post-SBRT PLR > 382.0 were negatively associated with shorter overall survival (OS). In the multivariate assessment, post-SBRT PLR > 382.0 was the only factor. Based on post-SBRT PLR, tumor locations, and tumor stage, we categorized patients into low, medium, or high-risk groups. CONCLUSIONS: Post-SBRT PLR > 382.0 correlated with survival in patients undergoing SBRT. The decision tree model might play a role in future risk stratification to guide the clinical practice of individualized SBRT for LA-NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inflamação , Neoplasias Pulmonares , Neutrófilos , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Masculino , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Idoso , Prognóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Neutrófilos/patologia , Inflamação/sangue , Linfócitos/patologia , Idoso de 80 Anos ou mais , Plaquetas/patologia , Contagem de Linfócitos , Contagem de Plaquetas , Taxa de Sobrevida/tendências , Estadiamento de Neoplasias , Biomarcadores Tumorais/sangue
6.
J Med Chem ; 67(5): 4194-4224, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38442261

RESUMO

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.


Assuntos
Corantes Fluorescentes , Células Th17 , Corantes Fluorescentes/farmacologia , Fatores de Transcrição , Regulação da Expressão Gênica , Polarização de Fluorescência , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo
7.
Front Psychol ; 15: 1293845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495419

RESUMO

Background: Positive psychology is a vibrant field of study, and conceptualizations of the components of well-being have received a great deal of attention from researchers. The study of well-being literacy thus provides an innovative perspective for enhancing and sustaining individuals' experiences of well-being. Objective: This study aimed to examine the psychometric properties of the wellbeing literacy 6-item (Well-Lit 6) scale in Chinese military academy cadets. Methods: A total of 3,218 undergraduate students from five military academies in China were recruited to complete questionnaires online. Results: (1) The items of the scale showed high discrimination; (2) The alpha coefficient of the scale was 0.986 and the split-half reliability was 0.981, indicating high homogeneous reliability and split-half reliability; (3) The scale model fitted well and displayed structural validity; (4) The correlation between well-being literacy and related indicators was significant, and the calibration correlation and convergent-discriminant validity of the scale were high; (5) After gradually adding demographic variables, known predictors factors and well-being literacy, the ∆R2 for subjective well-being, life satisfaction, depression, and anxiety ranged from 0.036 to 0.067, 0.184 to 0.340, and 0.009 to 0.017, respectively, showing high incremental validity; (6) the total well-being literacy scores differed significantly by gender, grade, and parenting style. Conclusion: The Chinese version of the Well-Lit 6 is reliable and valid in predicting and accessing the subjective well-being, life satisfaction, emotion regulation, and psychological resilience of Chinese military academy cadets.

8.
Plant Cell Physiol ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38545690

RESUMO

The miR390-derived TAS3 trans-acting short-interfering RNAs (tasiRNAs) module represents a conserved RNA silencing pathway in the plant kingdom; however, its characterization in the bryophyte Marchantia polymorpha is limited. This study elucidated that MpDCL4 processes MpTAS3 double-stranded RNA (dsRNA) to generate tasiRNAs, primarily from the 5'- and 3'-ends of dsRNA. Notably, we discovered a novel tasiRNA, tasi78A, can negatively regulate a cytochrome P450 gene, MpCYP78A101. Additionally, tasi78A was abundant in MpAGO1, and transient expression assays underscored the role of tasi78A in repressing MpCYP78A101. A microRNA, miR11700, also regulates MpCYP78A101 expression. This coordinate regulation suggests a role in modulating auxin signaling at apical notches of gemma, influencing the growth and sexual organ development of M. polymorpha and emphasizing the significance of RNA silencing in MpCYP78A101 regulation. However, phylogenetic analysis identified another paralog of the CYP78 family, Mp1g14150, which may have a redundant role with MpCYP78A101, explaining the absence of noticeable morphological changes in loss-of-function plants. Taken together, our findings provide new insights into the combined regulatory roles of miR390/MpTAS3/miR11700 in controlling MpCYP78A101 and expand our knowledge about the biogenesis and regulation of tasiRNAs in M. polymorpha.

9.
J Med Chem ; 67(6): 4346-4375, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38484122

RESUMO

Over the past decades, the role of rearranged during transfection (RET) alterations in tumorigenesis has been firmly established. RET kinase inhibition is an essential therapeutic target in patients with RET-altered cancers. In clinical practice, initial efficacy can be achieved in patients through the utilization of multikinase inhibitors (MKIs) with RET inhibitory activity. However, the effectiveness of these MKIs is impeded by the adverse events associated with off-target effects. Recently, many RET-selective inhibitors, characterized by heightened specificity and potency, have been developed, representing a substantial breakthrough in the field of RET precision oncology. This Perspective focuses on the contemporary understanding of RET mutations, recent advancements in next-generation RET inhibitors, and the challenges associated with resistance to RET inhibitors. It provides valuable insights for the development of next-generation MKIs and selective RET inhibitors.


Assuntos
Neoplasias Pulmonares , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteínas Proto-Oncogênicas c-ret/genética , Medicina de Precisão , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Neoplasias Pulmonares/tratamento farmacológico
11.
Nanotechnology ; 35(26)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38527361

RESUMO

Conjugated polymer-based organic/inorganic hybrid materials become the current research frontier and show great potential to integrate flexible polymers and rigid solid materials, which have been widely used in the field of various flexible electronics and optical devices. In this study, based on the multiple vapor phase infiltration (VPI) process, various precursor molecules (diethylzinc DEZ, trimethylaluminum TMA, H2O) are applied for thein situmodification of PBTTT-C14 films. The conductivity of the PBTTT-C14/Al2O3:ZnO (AZO) film is significantly enhanced, and the maximum value of conductivity is 1.16 S cm-1, which is eight orders of magnitude higher than the undoped PBTTT-C14 thin film. Here, the change of morphologies and crystalline states are analyzed via SEM, AFM, and XRD. And the chemical changes during the VPI process of PBTTT-C14 are characterized through Raman, XPS, and UV-vis. During the AZO VPI process, the formation of new ZnS matrix in the polymer subsurface can generate new additional electron conduction pathways through the crosslinking of polymer chains with inorganic materials, and the addition of Al2O3can bring about the increase of average grain size of ZnO crystals, which is also benefit to the conductivity increase of PBTTT-C14 thin film. Generally, the synergistic effect between the inorganic and polymer constituents results in the significantly enhancement of the conductivity of PBTTT-C14/AZO thin films.

12.
Exp Gerontol ; 189: 112408, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521178

RESUMO

BACKGROUND: Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role of eldecalcitol in the protection of osteocytes from senescence and the associated ferroptosis. METHODS: The MLO-Y4 osteocytes were exposed to D-gal inducing senescence. The ovariectomized (OVX) mice treated with D-gal using as an aging inducer were intraperitoneally injected with eldecalcitol. The multiplexed confocal imaging, fluorescence in situ hybridization and transmission electron microscopy were applied in assessing osteocytic properties. Immunochemical staining and immunoblotting were carried out to detect abundance and expression of molecules. RESULTS: The ablation of vitamin D receptor led to a reduction in amounts of osteocytes, a loss of dendrites, an increase in mRNA expression of SASP factors and in protein expression of senescent factors, as well as changes in mRNA expression of ferroptosis-related genes (PTGS2 & RGS4). Eldecalcitol reversed senescent phenotypes of MLO-Y4 cells shown by improving cell morphology and density, decreasing ß-gal-positive cell accumulation, and down-regulating protein expression (P16, P21 & P53). Eldecalcitol reduced intracellular ROS and MDA productions, elevated JC-1 aggregates, and up-regulated expression of Nrf2 and GPX4. Eldecalcitol exhibited osteopreserve effects in D-gal-induced aging OVX mice. The confocal imaging displayed its improvement on osteocytic network organization. Eldecalcitol decreased the numbers of senescent osteocytes at tibial diaphysis by SADS assay and attenuated mRNA expression of SASP factors as well as down-regulated protein expression of senescence-related factors and restored levels of ferroptotic biomarkers in osteocytes-enriched bone fraction. It reduced 4-HNE staining area, stimulated Nrf2-positive staining, and promoted nuclear translocation of Nrf2 in osteocytes of mice as well as inhibited and promoted protein expression of 4-HNE and Nrf2, respectively, in osteocytes-enriched bone fraction. CONCLUSIONS: The present study revealed the ameliorative effects of eldecalcitol on senescence and the associated ferroptosis of osteocytes, contributing to its preservation against osteoporosis of D-gal-induced senescent ovariectomized mice.


Assuntos
Ferroptose , Osteócitos , Vitamina D/análogos & derivados , Camundongos , Animais , Osteócitos/metabolismo , Hibridização in Situ Fluorescente , Fator 2 Relacionado a NF-E2/metabolismo , Vitamina D/metabolismo , RNA Mensageiro/metabolismo
13.
Vaccines (Basel) ; 12(2)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38400198

RESUMO

Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.

14.
Sci Rep ; 14(1): 4834, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418524

RESUMO

A large number of motor vehicles and non-motorized vehicles mixed in the section of arterial highway crossing the town leads to many traffic problems. Therefore, it is necessary to set up a side divider between motorized and non-motorized lanes, and the appropriate spacing of lateral crossing openings to meet the needs of non-motorized vehicles crossing the highway has become a key issue that must be resolved. This paper investigates the traffic flow characteristics of mixed traffic flow on arterial highways through small town sections, and from the two dimensions of highway access efficiency and the psychological characteristics of cyclists, it calibrates the setting range of the spacing of non-motorized lateral crossing openings under different design speeds, which is used to regulate the behavior of non-motorized vehicles crossing the street, improve the safety level of the highway, reduce the lateral interference of the highway, and improve the road access efficiency. The accuracy of the research results is verified by microscopic simulation experiments, which proves that they can meet good expectations in practical engineering. The research results have theoretical significance and reference value for improving the status quo of machine-non-mixed traffic in the section of arterial highway passing through small towns, and enhancing the efficiency and safety of highway traffic. It also provides corresponding reference for the areas facing similar problems worldwide.

15.
Chin J Integr Med ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386252

RESUMO

OBJECTIVE: To investigate the potential role of Tongxinluo (TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury (MIRI) in mice. METHODS: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups (n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril (BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition (EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1 (CD31), α-smoth muscle actin (α-SMA), phosphatidylinositol-3-kinase (PI3K) and phospho protein kinase B (p-AKT) were assessed using Western blot. RESULTS: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT (P<0.05 or P<0.01). TXL significantly increased the protein expressions of PI3K and p-AKT (P<0.05 or P<0.01). There was no significant difference between TXL and BNPL group (P>0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. CONCLUSION: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

16.
Bioorg Med Chem ; 100: 117631, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38330848

RESUMO

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.


Assuntos
Leucemia Mieloide Aguda , Tirosina Quinase 3 Semelhante a fms , Humanos , Apoptose , Linhagem Celular Tumoral , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Piridinas/farmacologia
17.
Neuroradiology ; 66(3): 409-416, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38191867

RESUMO

PURPOSE: Endovascular reconstruction has emerged as a viable alternative for carotid artery dissections (CADs) that are unresponsive to antithrombotic therapy. However, high cervical and long-segment CADs pose challenges during endovascular treatment due to their distal location and tortuous anatomy. We presented our experiences using endovascular reconstruction with the Leo plus stent for this type of CAD. METHODS: We conducted a retrospective review of patients with high cervical and long-segment CADs treated using the Leo plus stent. We analyzed patient demographics, clinical presentations, procedural features, complications, and follow-up outcomes. RESULTS: A total of 17 patients (mean age, 48.1 years) with 17 CADs were identified. Seven of these dissections were accompanied by pseudoaneurysm. The mean length of the dissection was 5.7 cm, and the mean degree of stenosis was 92.3%. A single Leo plus stent was deployed in 15 patients, while another Wallstent carotid stent was used in 2 cases. All stents were successfully positioned in their intended sites. The average degree of residual stenosis was 22.2%. There were no perioperative complications. With a median follow-up duration of 29 months, no ischemic stroke events occurred. All but one Leo plus stent remained patent during follow-up, and all 7 pseudoaneurysms had disappeared at the last radiological assessment. CONCLUSION: Our experience in treating high cervical and long-segment CADs with the Leo plus stent demonstrates that this approach is practical, safe, and effective, as evidenced by long-term observations. The Leo Plus stent appears to be a suitable option for managing this type of CAD.


Assuntos
Dissecção Aórtica , Dissecação da Artéria Carótida Interna , Procedimentos Endovasculares , Humanos , Pessoa de Meia-Idade , Dissecação da Artéria Carótida Interna/diagnóstico por imagem , Dissecação da Artéria Carótida Interna/cirurgia , Constrição Patológica/complicações , Resultado do Tratamento , Stents , Estudos Retrospectivos , Artérias Carótidas
18.
Biosens Bioelectron ; 248: 115999, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38183791

RESUMO

Global food systems can benefit significantly from continuous monitoring of microbial food safety, a task for which tedious operations, destructive sampling, and the inability to monitor multiple pathogens remain challenging. This study reports significant improvements to a paper chromogenic array sensor - machine learning (PCA-ML) methodology sensing concentrations of volatile organic compounds (VOCs) emitted on a species-specific basis by pathogens by streamlining dye selection, sensor fabrication, database construction, and machine learning and validation. This approach enables noncontact, time-dependent, simultaneous monitoring of multiple pathogens (Listeria monocytogenes, Salmonella, and E. coli O157:H7) at levels as low as 1 log CFU/g with over 90% accuracy. The report provides theoretical and practical frameworks demonstrating that chromogenic response, including limits of detection, depends on time integrals of VOC concentrations. The paper also discusses the potential for implementing PCA-ML in the food supply chain for different food matrices and pathogens, with species- and strain-specific identification.


Assuntos
Técnicas Biossensoriais , Listeria monocytogenes , Contagem de Colônia Microbiana , Microbiologia de Alimentos , Escherichia coli , Listeria monocytogenes/fisiologia , Carne
19.
Nat Commun ; 15(1): 289, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177169

RESUMO

The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images to create a 3D image stack. Precise and robust alignment in the presence of image artifacts is challenging, especially as datasets are attaining the petascale. We present a computational pipeline for aligning ssEM images with several key elements. Self-supervised convolutional nets are trained via metric learning to encode and align image pairs, and they are used to initialize iterative fine-tuning of alignment. A procedure called vector voting increases robustness to image artifacts or missing image data. For speedup the series is divided into blocks that are distributed to computational workers for alignment. The blocks are aligned to each other by composing transformations with decay, which achieves a global alignment without resorting to a time-consuming global optimization. We apply our pipeline to a whole fly brain dataset, and show improved accuracy relative to prior state of the art. We also demonstrate that our pipeline scales to a cubic millimeter of mouse visual cortex. Our pipeline is publicly available through two open source Python packages.


Assuntos
Encéfalo , Imageamento Tridimensional , Animais , Camundongos , Imageamento Tridimensional/métodos , Microscopia Eletrônica , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos
20.
Nutrition ; 119: 112298, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38176361

RESUMO

OBJECTIVES: Malnutrition has adverse postoperative outcomes, especially in emergency surgery. Among the numerous tools for nutritional assessment, this study aims to investigate malnutrition diagnosed by Global Leadership Initiative on Malnutrition criteria and the Global Leadership Initiative on Malnutrition predictive value for outcomes after emergency abdominal surgery. METHODS: This was a prospective observational study. Among the 468 patients undergoing emergency abdominal surgery admitted to a department of emergency surgery from June 2020 to December 2021, 53 patients were not eligible for enrollment, and 19 patients had missing data. Thus, the final number of participants was 396. Muscle mass was evaluated by skeletal muscle index at the third lumbar vertebra on computed tomography scans, and the lower quartile was defined as the threshold of muscle mass reduction. The associations of Global Leadership Initiative on Malnutrition, Global Leadership Initiative on Malnutrition (muscle mass reduction excluded), and skeletal muscle index with in-hospital mortality, postoperative complications, and postoperative stay were evaluated using χ2. In addition, confounding factors were screened, regression models were established, and the Global Leadership Initiative on Malnutrition predictive value was analyzed for clinical outcome. Ethical approval was obtained from the appropriate department. RESULTS: Malnutrition was observed in 19.9% of the total 396 patients based on the Global Leadership Initiative on Malnutrition and in 12.4% on the Global Leadership Initiative on Malnutrition (muscle mass reduction excluded). Sarcopenia by skeletal muscle index was found in 24.7% of patients. Univariate analysis indicated that in-hospital mortality, postoperative complications, infective complication rate, and postoperative hospital stay were significantly higher in malnourished and sarcopenic patients. Multivariate analysis found that malnutrition diagnosed by the Global Leadership Initiative on Malnutrition was predictive for complications, infective complications, and postoperative stay (total postoperative complications: odds ratio = 3.620; 95% CI, 1.635-8.015; P = 0.002; infective complications: odds ratio = 3.127; 95% CI, 1.194-8.192; P = 0.020; and postoperative stay: regression coefficient = 2.622; P = 0.022). The Global Leadership Initiative on Malnutrition (muscle mass reduction excluded) identified postoperative complications and postoperative stay (total postoperative complications: odds ratio = 3.364; 95% CI, 1.247-9.075; P = 0.017 and postoperative stay: regression coefficient = 3.547; P = 0.009). Sarcopenia by skeletal muscle index was a risk factor for postoperative complications (odds ratio = 3.366; 95% CI, 1.587-7.140; P = 0.002). CONCLUSION: The Global Leadership Initiative on Malnutrition and Global Leadership Initiative on Malnutritison (muscle mass reduction excluded) had predictive value for adverse clinical outcomes due to malnutrition in patients undergoing emergency abdominal surgery.


Assuntos
Desnutrição , Sarcopenia , Humanos , Liderança , Sarcopenia/diagnóstico , Prognóstico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Desnutrição/diagnóstico , Avaliação Nutricional , Estado Nutricional
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