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1.
Sci Rep ; 14(1): 14368, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909046

RESUMO

As urban development accelerates and natural disasters occur more frequently, the urgency of developing effective emergency shelter planning strategies intensifies. The shelter location selection method under the traditional multi-criteria decision-making framework suffers from issues such as strong subjectivity and insufficient data support. Artificial intelligence offers a robust data-driven approach for site selection; however, many methods neglect the spatial relationships of site selection targets within geographical space. This paper introduces an emergency shelter site selection model that combines a variational graph autoencoder (VGAE) with a random forest (RF), namely VGAE-RF. In the constructed urban spatial topological graph, based on network geographic information, this model captures both the latent features of geographic unit coupling and integrates explicit and latent features to forecast the likelihood of emergency shelters in the construction area. This study takes Beijing, China, as the experimental area and evaluates the reliability of different model methods using a confusion matrix, Receiver Operating Characteristic (ROC) curve, and Imbalance Index of spatial distribution as evaluation indicators. The experimental results indicate that the proposed VGAE-RF model method, which considers spatial semantic associations, displays the best reliability.

2.
Int J Biol Macromol ; 271(Pt 1): 132472, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772455

RESUMO

The two most active disulfide bond isomers of the analgesic αO-conotoxin GeXIVA, namely GeXIVA[1, 2] and GeXIVA[1, 4], were subjected to Asp-scanning mutagenesis to determine the key amino acid residues for activity at the rat α9α10 nicotinic acetylcholine receptor (nAChR). These studies revealed the key role of arginine residues for the activity of GeXIVA isomers towards the α9α10 nAChR. Based on these results, additional analogues with 2-4 mutations were designed and tested. The analogues [T1A,D14A,V28K]GeXIVA[1, 2] and [D14A,I23A,V28K]GeXIVA[1, 4] were developed and showed sub-nanomolar activity for the α9α10 nAChR with IC50 values of 0.79 and 0.38 nM. The latter analogue had exceptional selectivity for the α9α10 receptor subtype over other nAChR subtypes and can be considered as a drug candidate for further development. Molecular dynamics of receptor-ligand complexes allowed us to make deductions about the possible causes of increases in the affinity of key GeXIVA[1, 4] mutants for the α9α10 nAChR.


Assuntos
Arginina , Ácido Aspártico , Conotoxinas , Receptores Nicotínicos , Conotoxinas/química , Conotoxinas/genética , Conotoxinas/farmacologia , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química , Animais , Arginina/química , Ratos , Ácido Aspártico/química , Ácido Aspártico/genética , Antagonistas Nicotínicos/química , Antagonistas Nicotínicos/farmacologia , Simulação de Dinâmica Molecular , Mutagênese , Isomerismo
3.
J Acoust Soc Am ; 155(5): 2959-2972, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717203

RESUMO

Frequency hopping (FH) signals have been widely used to improve performance against frequency selective fading phenomenon of underwater channels. However, the channel is slowly varying in regard to changes in weather conditions, and thus the conventional FH detection transmitting signals with fixed frequency cannot guarantee good detection performance in the dynamic underwater environment. To overcome the performance degradation in slowly-varying fading dispersive channels, this paper proposes an adaptive frequency-hopping (AFH) target detection method. Compared with conventional FH detection methods, the AFH can adaptively select the optimal detection frequency based on premeasured background noise and channel frequency response measured from previous experiments. Numerical simulations and lake trials are conducted to verify the effectiveness of the AFH. The simulation results show that the AFH has better detection performance than the conventional FH. The lake trial results have also verified the validity and feasibility of AFH. Importantly, AFH also achieves a better output signal-to-noise ratio under actual noise interference.

4.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38612384

RESUMO

3-methyl-4-nitrophenol (PNMC), a well-known constituent of diesel exhaust particles and degradation products of insecticide fenitrothion, is a widely distributed environmental contaminant. PNMC is toxic to the female reproductive system; however, how it affects meiosis progression in oocytes is unknown. In this study, in vitro maturation of mouse oocytes was applied to investigate the deleterious effects of PNMC. We found that exposure to PNMC significantly compromised oocyte maturation. PNMC disturbed the spindle stability; specifically, it decreased the spindle density and increased the spindle length. The weakened spindle pole location of microtubule-severing enzyme Fignl1 may result in a defective spindle apparatus in PNMC-exposed oocytes. PNMC exposure induced significant mitochondrial dysfunction, including mitochondria distribution, ATP production, mitochondrial membrane potential, and ROS accumulation. The mRNA levels of the mitochondria-related genes were also significantly impaired. Finally, the above-mentioned alterations triggered early apoptosis in the oocytes. In conclusion, PNMC exposure affected oocyte maturation and quality through the regulation of spindle stability and mitochondrial function.


Assuntos
Doenças Mitocondriais , Oócitos , Feminino , Animais , Camundongos , Cresóis , DNA Mitocondrial , Meiose
5.
Vet Microbiol ; 291: 110034, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432076

RESUMO

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.


Assuntos
Vírus da Diarreia Viral Bovina Tipo 1 , Vírus da Diarreia Viral Bovina , Bovinos , Animais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Vírus da Diarreia Viral Bovina/fisiologia , Linfócitos T CD8-Positivos , Ácidos Graxos , Lipídeos
6.
Nat Commun ; 15(1): 2778, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555361

RESUMO

Bacterial genotoxins damage host cells by targeting their chromosomal DNA. In the present study, we demonstrate that a genotoxin of Salmonella Typhi, typhoid toxin, triggers the senescence-associated secretory phenotype (SASP) by damaging mitochondrial DNA. The actions of typhoid toxin disrupt mitochondrial DNA integrity, leading to mitochondrial dysfunction and disturbance of redox homeostasis. Consequently, it facilitates the release of damaged mitochondrial DNA into the cytosol, activating type I interferon via the cGAS-STING pathway. We also reveal that the GCN2-mediated integrated stress response plays a role in the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect on T cells, leading to senescence in these cells. These findings provide insights into how a bacterial genotoxin targets mitochondria to trigger a proinflammatory SASP, highlighting a potential therapeutic target for an anti-toxin intervention.


Assuntos
Fenótipo Secretor Associado à Senescência , Febre Tifoide , Humanos , Febre Tifoide/metabolismo , Mutagênicos/metabolismo , Senescência Celular/fisiologia , Mitocôndrias/metabolismo , DNA Mitocondrial/metabolismo , Salmonella , Fenótipo
7.
Comput Biol Med ; 172: 108244, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38457931

RESUMO

The primary objective of this study is to enhance the prediction accuracy of intradialytic hypotension in patients undergoing hemodialysis. A significant challenge in this context arises from the nature of the data derived from the monitoring devices and exhibits an extreme class imbalance problem. Traditional predictive models often display a bias towards the majority class, compromising the accuracy of minority class predictions. Therefore, we introduce a method called UnderXGBoost. This novel methodology combines the under-sampling, bagging, and XGBoost techniques to balance the dataset and improve predictive accuracy for the minority class. This method is characterized by its straightforward implementation and training efficiency. Empirical validation in a real-world dataset confirms the superior performance of UnderXGBoost compared to existing models in predicting intradialytic hypotension. Furthermore, our approach demonstrates versatility, allowing XGBoost to be substituted with other classifiers and still producing promising results. Sensitivity analysis was performed to assess the model's robustness, reinforce its reliability, and indicate its applicability to a broader range of medical scenarios facing similar challenges of data imbalance. Our model aims to enable medical professionals to provide preemptive treatments more effectively, thereby improving patient care and prognosis. This study contributes a novel and effective solution to a critical issue in medical prediction, thus broadening the application spectrum of predictive modeling in the healthcare domain.


Assuntos
Hipotensão , Humanos , Reprodutibilidade dos Testes , Hipotensão/etiologia , Diálise Renal/efeitos adversos , Diálise Renal/métodos
8.
Medicine (Baltimore) ; 103(5): e37092, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306570

RESUMO

Pancreatic adenocarcinoma is the most common malignant tumor of the digestive system and is called the "king of cancer" because it has been labeled with high malignancy, rapid progression, poor survival, and poor prognosis. Previously, it was reported that the basic leucine zipper and W2 domains 1 (BZW1) is involved in the progression of many tumors. However, its research in digestive system tumors such as pancreatic cancer is rarely studied. To explore potential biomarkers related to survival and prognosis of pancreatic cancer and provide a new targeted therapy for it. We first analyzed the mRNA and protein expression of BZW1 in pancreatic cancer. We then explored the correlation of BZW1 with survival prognosis and immune infiltration in pancreatic cancer patients. Finally, we explored BZW1-related gene enrichment analysis, including protein-protein interaction networks, gene ontology functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The mRNA and protein expression of the BZW1 gene in pancreatic cancer tissues were higher than those in adjacent normal tissues, and pancreatic cancer patients with high BZW1 expression had a poor prognosis. In addition, the expression of BZW1 was positively or negatively correlated with different immune cells of pancreatic cancer, such as CD4 + T lymphocytes, CD8 + T lymphocytes, B cells, macrophages, neutrophils, etc. Correlation enrichment analysis showed that we obtained 50 available experimentally determined BZW1-binding proteins and 100 targeted genes related to BZW1, and the intersection genes were eukaryotic translation termination factor 1 and Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3. Moreover, there was a positive correlation between BZW1 and eukaryotic translation termination factor 1 and Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 genes in pancreatic cancer. Gene ontology enrichment analysis showed BZW1 was mainly related to biological processes such as "mRNA processing," "RNA splicing," "regulation of translational initiation," and "activation of innate immune response." The results of Kyoto Encyclopedia of Genes and Genomes pathway analysis further indicated that BZW1 may be involved in pancreatic carcinogenesis through the "spliceosome" and "ribosome." The BZW1 gene may be a potential immunotherapy target and a promising prognostic marker for pancreatic cancer.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Prognóstico , Neoplasias Pancreáticas/genética , Adenocarcinoma/genética , Biomarcadores , Peptídeos , RNA Mensageiro , Nucleotídeos de Guanina , Proteínas de Ligação a DNA , Proteínas de Ciclo Celular
9.
Biotechnol Bioeng ; 121(5): 1583-1595, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38247359

RESUMO

As a non-destructive sensing technique, Raman spectroscopy is often combined with regression models for real-time detection of key components in microbial cultivation processes. However, achieving accurate model predictions often requires a large amount of offline measurement data for training, which is both time-consuming and labor-intensive. In order to overcome the limitations of traditional models that rely on large datasets and complex spectral preprocessing, in addition to the difficulty of training models with limited samples, we have explored a genetic algorithm-based semi-supervised convolutional neural network (GA-SCNN). GA-SCNN integrates unsupervised process spectral labeling, feature extraction, regression prediction, and transfer learning. Using only an extremely small number of offline samples of the target protein, this framework can accurately predict protein concentration, which represents a significant challenge for other models. The effectiveness of the framework has been validated in a system of Escherichia coli expressing recombinant ProA5M protein. By utilizing the labeling technique of this framework, the available dataset for glucose, lactate, ammonium ions, and optical density at 600 nm (OD600) has been expanded from 52 samples to 1302 samples. Furthermore, by introducing a small component of offline detection data for recombinant proteins into the OD600 model through transfer learning, a model for target protein detection has been retrained, providing a new direction for the development of associated models. Comparative analysis with traditional algorithms demonstrates that the GA-SCNN framework exhibits good adaptability when there is no complex spectral preprocessing. Cross-validation results confirm the robustness and high accuracy of the framework, with the predicted values of the model highly consistent with the offline measurement results.


Assuntos
Escherichia coli , Redes Neurais de Computação , Fermentação , Escherichia coli/genética , Algoritmos , Proteínas Recombinantes/genética
10.
Heart Rhythm ; 21(2): 184-196, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37924963

RESUMO

BACKGROUND: More than a hundred genetic loci have been associated with atrial fibrillation (AF). But the exact mechanism remains unclear and the treatment needs to be improved. OBJECTIVE: This study aimed to investigate the mechanism and potential treatment of NPPA mutation-associated AF. METHODS: Nppa knock-in (KI, p.I137T) rats were generated, and cardiac function was evaluated. Blood pressure was recorded using a tail-cuff system. The expression levels were measured using real-time polymerase chain reaction, enzyme-linked immunosorbent assay or Western blot analysis, and RNA-sequence analysis. Programmed electrical stimulation, patch clamp, and multielectrode array were used to record the electrophysical characteristics. RESULTS: Mutant rats displayed downregulated expression of atrial natriuretic peptide but elevated blood pressure and enlarged left atrial end-diastolic diameter. Further, gene topology analysis suggested that the majority of differently expressed genes in Nppa KI rats were related to inflammation, electrical remodeling, and structural remodeling. The expression levels of C-C chemokine ligand 5 and galectin-3 involved in remodeling were higher, while there were declined levels of Nav1.5, Cav1.2, and connexin 40. AF was more easily induced in KI rats. Electrical remodeling included abbreviated action potentials, effective refractory period, increased late sodium current, and reduced calcium current, giving rise to conduction abnormalities. These electrophysiological changes could be reversed by the late sodium current blocker ranolazine and the Nav1.8 blocker A-803467. CONCLUSION: Our findings suggest that structural remodeling related to inflammation and fibrosis and electrical remodeling involved in late sodium current underly the major effects of the Nppa (p.I137T) variant to induce AF, which can be attenuated by the late sodium current blocker and Nav1.8 blocker.


Assuntos
Fibrilação Atrial , Remodelamento Atrial , Procainamida , Animais , Ratos , Potenciais de Ação/fisiologia , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Fator Natriurético Atrial , Remodelamento Atrial/fisiologia , Átrios do Coração , Inflamação/metabolismo , Mutação , Miócitos Cardíacos/metabolismo , Procainamida/análogos & derivados , Sódio/metabolismo
11.
Phys Rev Lett ; 131(7): 073401, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37656862

RESUMO

Ultracold atoms in optical lattices form a competitive candidate for quantum computation owing to the excellent coherence properties, the highly parallel operations over spins, and the ultralow entropy achieved in qubit arrays. For this, a massive number of parallel entangled atom pairs have been realized in superlattices. However, the more formidable challenge is to scale up and detect multipartite entanglement, the basic resource for quantum computation, due to the lack of manipulations over local atomic spins in retroreflected bichromatic superlattices. In this Letter, we realize the functional building blocks in quantum-gate-based architecture by developing a cross-angle spin-dependent optical superlattice for implementing layers of quantum gates over moderately separated atoms incorporated with a quantum gas microscope for single-atom manipulation and detection. Bell states with a fidelity of 95.6(5)% and a lifetime of 2.20±0.13 s are prepared in parallel, and then connected to multipartite entangled states of one-dimensional ten-atom chains and two-dimensional plaquettes of 2×4 atoms. The multipartite entanglement is further verified with full bipartite nonseparability criteria. This offers a new platform toward scalable quantum computation and simulation.

12.
J Orthop Traumatol ; 24(1): 51, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735320

RESUMO

BACKGROUND: Percutaneous iliosacral (IS) screw fixation and trans-iliac trans-sacral (TITS) screw fixation are clinically effective treatments of posterior pelvic sacroiliac fractures. In order to accurately assess the sacrum position relative to the pelvis, pelvic incidence (PI) is a commonly utilized radiographic parameter in sagittal view. This study aimed to investigate and compare the surgical outcomes and radiographic parameters of IS or TITS screw fixations for the treatment of posterior sacroiliac complex fractures with different PI values. MATERIALS AND METHODS: The data on patients with posterior pelvic sacroiliac fractures who underwent percutaneous IS or TITS screw fixations, or both, at a single level I trauma center between January 2017 and June 2020 were reviewed. We documented the patient characteristics and fracture types, reviewed surgical records, and measured the radiographic parameters via plain films and multi-planar computed tomography (mpCT) images. Radiographic variations in PI, sacral slope, pelvic tilt, sacral dysmorphism, pelvic ring reduction quality, screw deviation angles, screw malposition grading, and iatrogenic complications were documented and analyzed. RESULTS: A total of 85 patients were included, and 65 IS and 70 TITS screws were accounted for. Patients were divided into two groups according to screw fixation method and further divided into four sub-groups based on baseline PI values. The PI cutoff values were 49.85° and 48.05° in the IS and TITS screw groups, respectively, according to receiver operating characteristic analysis and Youden's J statistic. Smaller PI values were significantly correlated with sacral dysmorphism (p = 0.027 and 0.003 in the IS and TITS screw groups, respectively). Patients with larger PI values were at a significantly increased risk of screw malposition in the TITS screw group (p = 0.049), with no association in the IS screw group. Logistic regression confirmed that a larger PI value was a significant risk factor for screw malposition in the TITS screw group (p = 0.010). The post-operative outcomes improved from poor/fair (at 6 months) to good/average (at 12 months) based on the Postel Merle d'Aubigné and Majeed scores, with no significant differences between subgroups. CONCLUSIONS: Both percutaneous IS and TITS screw fixations are safe and effective treatments for posterior pelvic sacroiliac fractures. Due to the higher risk of screw malposition in patients with larger PI values, it is crucial to identify potential patients at risk when performing TITS screw fixation surgery. LEVEL OF EVIDENCE: Level III.


Assuntos
Fraturas Ósseas , Sacro , Humanos , Sacro/diagnóstico por imagem , Sacro/cirurgia , Parafusos Ósseos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Período Pós-Operatório , Postura
13.
Clin Hypertens ; 29(1): 26, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37777810

RESUMO

BACKGROUND: The relationship between the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphism (SNP) and serum homocysteine (Hcy) levels or H-type hypertension in different populations is inconsistent. This study aimed to explore the association between the MTHFR rs1801133 SNP and serum Hcy levels of Zhuang hypertensive patients in the central region of Guangxi. METHODS: A total of 606 Zhuang inpatients with essential hypertension were recruited in our hospital from August 2016 to December 2018. The patients were divided into H-type hypertension (Hcy > 10 µmol/L, n = 528) and non-H-type hypertension (Hcy ≤ 10 µmol/L, n = 78) groups. At the same time, an age- and sex-matched group of 379 subjects with normal physical examination in our hospital were selected as the control group. Blood biochemical measurements and genotyping of the MTHFR rs1801133 SNP were performed. RESULTS: The prevalence of H-type hypertension was 87.13%. The levels of serum Hcy in patients with hypertension were higher than those in control group (14.20 ± 5.78 µmol/L vs. 11.97 ± 5.39 µmol/L, P < 0.001), especially in patients with H-type hypertension (15.08 ± 5.65 µmol/L, P < 0.001). The frequencies of TT genotype (22.73%) and T allele (46.21%) in patients with H-type hypertension were significantly higher than those in control group (11.35% and 30.47%, respectively) and non-H-type hypertension group (10.26% and 28.85%, respectively; P < 0.001 for all). Multivariate linear regression analysis showed that serum Hcy levels were significantly correlated with creatinine, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, and the MTHFR rs1801133 genotypes in control group, while serum Hcy levels were significantly correlated with creatinine, triglyceride, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, glycosylated hemoglobin, and the MTHFR rs1801133 genotypes in H-type hypertension group (P < 0.05-0.001). Serum Hcy levels in the T allele carriers were higher than those in the T allele noncarriers in both H-type hypertension and control groups. CONCLUSIONS: There was closely related between the MTHFR rs1801133 SNP and serum Hcy levels in Zhuang patients with H-type hypertension in the central region of Guangxi. The MTHFR SNP may be an important reason for the increase of serum Hcy levels in Zhuang patients with H-type hypertension in this region.

14.
Int J Mol Sci ; 24(15)2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37569830

RESUMO

The ten-eleven translocation (TET) enzyme family, which includes TET1/2/3, participates in active DNA demethylation in the eukaryotic genome; moreover, TET1/2/3 are functionally redundant in mice embryos. However, the combined effect of TET1/2/3 triple-gene knockdown or knockout on the porcine oocytes or embryos is still unclear. In this study, using Bobcat339, a specific small-molecule inhibitor of the TET family, we explored the effects of TET enzymes on oocyte maturation and early embryogenesis in pigs. Our results revealed that Bobcat339 treatment blocked porcine oocyte maturation and triggered early apoptosis. Furthermore, in the Bobcat339-treated oocytes, spindle architecture and chromosome alignment were disrupted, probably due to the huge loss of 5-hydroxymethylcytosine (5hmC)and concurrent increase in 5-methylcytosine (5mC). After Bobcat339 treatment, early parthenogenetic embryos exhibited abnormal 5mC and 5hmC levels, which resulted in compromised cleavage and blastocyst rate. The mRNA levels of EIF1A and DPPA2 (ZGA marker genes) were significantly decreased, which may explain why the embryos were arrested at the 4-cell stage after Bobcat339 treatment. In addition, the mRNA levels of pluripotency-related genes OCT4 and NANOG were declined after Bobcat339 treatment. RNA sequencing analysis revealed differentially expressed genes in Bobcat339-treated embryos at the 4-cell stage, which were significantly enriched in cell proliferation, cell component related to mitochondrion, and cell adhesion molecule binding. Our results indicated that TET proteins are essential for porcine oocyte maturation and early embryogenesis, and they act by mediating 5mC/5hmC levels and gene transcription.

15.
Zhongguo Zhen Jiu ; 43(8): 876-80, 2023 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-37577881

RESUMO

Jingjin (muscle region of meridian) is a distal diagnosis and treatment system of the sinew/fascia disorders on the base of the concept of jin in TCM. Jin should be a particular palpable structure rather than a single anatomic structure with a specific distributing course. Yizhi weishu refers to a idea running through the whole process of diagnosis and treatment of sinew/fascia disorders, in which, the results, obtained by the overall observation and palpation of patient's sinew/fascia structure, are taken as the criteria of treatment. Yitong weishu (taking the sites of sensitivity or tenderness as the points) verifies this idea in practice. Under the guidance of yizhi weishu, through identifying the primary from the secondary, and regulating yin and yang, the spasticity and flaccidity of sinews/fascia can be cured and the induced diseases treated. The diagnosis and treatment system of jingjin, based on yizhi weishu, develops the original jingjin theory with vague concept involved, formulates a systematic thinking of treatment for sinew/fascia disorders and provides a new approach to clinical treatment.


Assuntos
Terapia por Acupuntura , Meridianos , Humanos , Espasticidade Muscular
16.
Nat Commun ; 14(1): 1903, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37019934

RESUMO

The synthesis of the cell-wall peptidoglycan during bacterial cell division is mediated by a multiprotein machine, called the divisome. The essential membrane protein complex of FtsB, FtsL and FtsQ (FtsBLQ) is at the heart of the divisome assembly cascade in Escherichia coli. This complex regulates the transglycosylation and transpeptidation activities of the FtsW-FtsI complex and PBP1b via coordination with FtsN, the trigger for the onset of constriction. Yet the underlying mechanism of FtsBLQ-mediated regulation is largely unknown. Here, we report the full-length structure of the heterotrimeric FtsBLQ complex, which reveals a V-shaped architecture in a tilted orientation. Such a conformation could be strengthened by the transmembrane and the coiled-coil domains of the FtsBL heterodimer, as well as an extended ß-sheet of the C-terminal interaction site involving all three proteins. This trimeric structure may also facilitate interactions with other divisome proteins in an allosteric manner. These results lead us to propose a structure-based model that delineates the mechanism of the regulation of peptidoglycan synthases by the FtsBLQ complex.


Assuntos
Proteínas de Escherichia coli , Proteínas de Escherichia coli/metabolismo , Proteínas de Ciclo Celular/metabolismo , Peptidoglicano/metabolismo , Proteínas de Membrana/metabolismo , Divisão Celular , Escherichia coli/metabolismo , Proteínas de Bactérias/metabolismo
17.
Retina ; 43(5): 767-774, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36727822

RESUMO

PURPOSE: To develop a deep convolutional neural network that enables the prediction of postoperative visual outcomes after epiretinal membrane surgery based on preoperative optical coherence tomography images and clinical parameters to refine surgical decision making. METHODS: A total of 529 patients with idiopathic epiretinal membrane who underwent standard vitrectomy with epiretinal membrane peeling surgery by two surgeons between January 1, 2014, and June 1, 2020, were enrolled. The newly developed Heterogeneous Data Fusion Net was introduced to predict postoperative visual acuity outcomes (improvement ≥2 lines in Snellen chart) 12 months after surgery based on preoperative cross-sectional optical coherence tomography images and clinical factors, including age, sex, and preoperative visual acuity. The predictive accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network model were evaluated. RESULTS: The developed model demonstrated an overall accuracy for visual outcome prediction of 88.68% (95% CI, 79.0%-95.7%) with an area under the receiver operating characteristic curve of 97.8% (95% CI, 86.8%-98.0%), sensitivity of 87.0% (95% CI, 67.9%-95.5%), specificity of 92.9% (95% CI, 77.4%-98.0%), precision of 0.909, recall of 0.870, and F1 score of 0.889. The heatmaps identified the critical area for prediction as the ellipsoid zone of photoreceptors and the superficial retina, which was subjected to tangential traction of the proliferative membrane. CONCLUSION: The novel Heterogeneous Data Fusion Net demonstrated high accuracy in the automated prediction of visual outcomes after weighing and leveraging multiple clinical parameters, including optical coherence tomography images. This approach may be helpful in establishing personalized therapeutic strategies for epiretinal membrane management.


Assuntos
Membrana Epirretiniana , Humanos , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Estudos Transversais , Retina/diagnóstico por imagem , Prognóstico , Acuidade Visual , Vitrectomia/métodos , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos
18.
Drug Test Anal ; 15(10): 1156-1163, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35712913

RESUMO

Use of electronic cigarettes (e-cigarettes) has increased significantly over the past decade due to consumer perception that these products represent a less risky alternative to combustible cigarettes. E-liquids generally contain a simple mix of vegetable glycerin, propylene glycerol, nicotine, organic acids, and flavourings. Regulators require that harmful and potentially harmful constituents (HPHCs) that might cause harm to the consumer must be monitored in the aerosol generated by e-cigarettes and in cigarette smoke (CS). To quantify HPHCs in aerosols from commercial flavoured e-cigarettes in Chinese market, this study has systematically compared levels of HPHCs, including eight carbonyls, five volatile organic compounds, four tobacco-specific nitrosamines, 16 polycyclic aromatic hydrocarbons, and seven heavy metals, in the aerosols of four market-leading flavoured e-cigarettes and mainstream CS, alongside in vitro cytotoxicity and mutagenicity assays. The vast majority of HPHCs were either undetected or significantly lower in the e-cigarette aerosols than in commercial CS or reference CS (3R4F). Where HPHCs were detected, there were small variations among the different flavoured e-cigarettes. In the neutral red uptake and Ames assays, aqueous extracts of the e-cigarette aerosols did not induce obvious cytotoxicity or mutagenicity, whereas CS aqueous extract showed dose-related cytotoxicity and mutagenicity. Collectively, these results indicate that use of e-cigarettes might potentially lead to a significant reduction in exposure to harmful substances, with fewer cytotoxic and mutagenic effects, as compared with conventional smoking. Further studies based on human puffing conditions and longer evaluation periods will be needed to substantiate this potential.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Produtos do Tabaco/análise , Nicotina/análise , Aerossóis/toxicidade , Nicotiana
19.
Sci Rep ; 12(1): 19404, 2022 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371412

RESUMO

Whilst the majority of the literature suggests that balloon kyphoplasty (BKP) can relieve pain associated with vertebral compression fractures (VCFs), evidence of high-viscosity cement (HVC) vertebroplasty (VP) or low viscosity cement (LVC) BKP for the treatment of VCFs at the levels of high and mid-thoracic vertebrae remains limited. The purpose of this study was to identify the different outcomes between HVC VP and LVC BKP used to repair high (T4-6) and mid (T7-9)-thoracic VCFs. A total of 114 patients with painful collapsed single-level vertebrae at high to mid-thoracic level who had undergone HVC VP or LVC BKP at a single tertiary medical center was reviewed retrospectively. All patients were divided into the HVC VP group (n = 72) and the LVC BKP group (n = 42). Clinical outcomes including demographic data and visual analogue scale (VAS) were compared. Radiographic data were collected preoperatively, postoperatively, and at final follow-up. More volume (ml) of cement injection was seen in the LVC BKP group (4.40 vs. 3.66, p < 0.001). The operation time (minutes) of the HVC VP group was significantly less than that of the LVC BKP group (33.34 vs. 39.05, p = 0.011). Leakage rate of cement was also fewer in the HVC VP group (26/72 vs. 27/42, p = 0.004). Compared with preoperative data, the VAS was improved after surgery in both groups. The LVC BKP group corrected more middle vertebral body height and local kyphosis angle than the HVC VP group. The outcomes of LVC BKP were not superior to that of HVC VP. HVC VP might be a good alternative to LVC BKP in the treatment of osteoporotic VCFs in high to mid-thoracic spine.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Fraturas por Compressão/cirurgia , Fraturas por Compressão/tratamento farmacológico , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/tratamento farmacológico , Viscosidade , Estudos Retrospectivos , Fraturas por Osteoporose/cirurgia , Cimentos Ósseos/uso terapêutico , Vértebras Torácicas/cirurgia , Dor/tratamento farmacológico , Cimentos de Ionômeros de Vidro , Resultado do Tratamento
20.
Sensors (Basel) ; 22(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36236693

RESUMO

There is a critical need for detection of administrative regions through network map pictures in map censorship tasks, which can be implemented by target detection technology. However, on map images there tend to be numerous administrative regions overlaying map annotations and symbols, thus making it difficult to accurately detect each region. Using a RetinaNet-based target detection model integrating ResNet50 and a feature pyramid network (FPN), this study built a multi-target model and a single-target cascading model from three single-target models by taking Taiwan, Tibet, and the Chinese mainland as target examples. Two models were evaluated both in classification and localization accuracy to investigate their administrative region detection performance. The results show that the single-target cascading model was able to detect more administrative regions, with a higher f1_score of 0.86 and mAP of 0.85 compared to the multi-target model (0.56 and 0.52, respectively). Furthermore, location box size distribution from the single-target cascading model looks more similar to that of manually annotated box sizes, which signifies that the proposed cascading model is superior to the multi-target model. This study is promising in providing support for computer map reading and intelligent map censorship.


Assuntos
Inteligência , Taiwan
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