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Photic niche shifts of mammals are associated with changing visual capabilities, primarily mediated by three visual pigments, two (SWS1 and M/LWS) of them for color vision and rhodopsin (RH1) for dim-light vision. To further elucidate molecular mechanisms of mammalian visual adaptations to different light environments, a systematic study incorporating evolutionary analyses across diverse groups and in vitro assays have been carried out. Here, we collected gene sequences for the three opsins from 220 species covering all major mammalian clades. After screening for cone opsin gene losses, we estimated selective pressures on each of the three genes and compared the levels of selection experienced by species living in bright- and dim-light environments. SWS1 pigment is shown to experience accelerated evolution in species living in bright-light environments as has RH1 in aquatic cetaceans, indicating potential shifts for ecological adaptations. To further elucidate the functional mechanisms for these two pigments, we then carried out site-directed mutagenesis in representative taxa. For SWS1, violet and ultraviolet sensitivities in the pika and mouse are mainly affected by substitutions at the critical sites 86 and 93, which have strong epistatic interaction. For RH1, the phenotypic difference between the sperm whale and bovine sequences is largely contributed by a substitution at site 195, which could be critical for dim-light sensation for deep-diving species. Different evolutionary patterns for the visual pigments have been identified in mammals, which correspond to photic niches, although additional phenotypic assays are still required to fully explain the functional mechanisms.
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Evolução Molecular , Mamíferos , Animais , Bovinos , Camundongos , Filogenia , Opsinas/genética , Rodopsina/genéticaRESUMO
High-sensitive uncooled mid-wave infrared (MWIR) photodetection with fast speed is highly desired for biomedical imaging, optical communication, and night vision technology. Low-dimensional materials with low dark current and broadband photoresponse hold great promise for use in MWIR detection. Here, this study reports a high-performance MWIR photodetector based on a titanium trisulfide (TiS3) nanoribbon. This device demonstrates an ultra-broadband photoresponse ranging from the visible spectrum to the MWIR spectrum (405-4275 nm). In the MWIR spectral range, the photodetector achieves competitive high photoresponsivity (R) of 21.1 A W-1, and an impressive specific detectivity (D*) of 5.9 × 1010 cmHz1/2 W-1 in ambient air. Remarkably, the photoresponse speed in the MWIR with τr = 1.3 ms and τd = 1.5 ms is realized which is much faster than the thermal time constant of 15 ms. These findings pave the way for highly sensitive, room-temperature MWIR photodetectors with exceptionally fast response speed.
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The highly selective electrochemical conversion of methanol to formate is of great significance for various clean energy devices, but understanding the structure-to-property relationship remains unclear. Here, the asymmetric charge polarized NiCo prussian blue analogue (NiCo PBA-100) is reported to exhibit remarkable catalytic performance with high current density (210 mA cm-2 @1.65 V vs RHE) and Faraday efficiency (over 90%). Meanwhile, the hybrid water splitting and Zinc-methanol-battery assembled by NiCo PBA-100 display the promoted performance with decent stability. X-ray absorption spectroscopy (XAS) and operando Raman spectroscopy indicate that the asymmetric charge polarization in NiCo PBA leads to more unoccupied states of Ni and occupied states of Co, thereby facilitating the rapid transformation of the high-active catalytic centers. Density functional theory calculations combining operando Fourier transform infrared spectroscopy demonstrate that the final reconstructed catalyst derived by NiCo PBA-100 exhibits rearranged d band properties along with a lowered energy barrier of the rate-determining step and favors the desired formate production.
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BACKGROUND: Accurately predicting the walking independence of stroke patients is important. Our objective was to determine and compare the performance of logistic regression (LR) and three machine learning models (eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), and Random Forest (RF)) in predicting walking independence at discharge in stroke patients, as well as to explore the variables that predict prognosis. METHODS: 778 (80% for the training set and 20% for the test set) stroke patients admitted to China Rehabilitation Research Center between February 2020 and January 2023 were retrospectively included. The training set was used for training models. The test set was used to validate and compare the performance of the four models in terms of area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. RESULTS: Among the three ML models, the AUC of the XGBoost model is significantly higher than that of the SVM and RF models (P < 0.001, P = 0.024, respectively). There was no significant difference in the AUCs between the XGBoost model and the LR model (0.891 vs. 0.880, P = 0.560). The XGBoost model demonstrated superior accuracy (87.82% vs. 86.54%), sensitivity (50.00% vs. 39.39%), PPV (73.68% vs. 73.33%), NPV (89.78% vs. 87.94%), and F1 score (59.57% vs. 51.16%), with only slightly lower specificity (96.09% vs. 96.88%). Together, the XGBoost model and the stepwise LR model identified age, FMA-LE at admission, FAC at admission, and lower limb spasticity as key factors influencing independent walking. CONCLUSION: Overall, the XGBoost model performed best in predicting independent walking after stroke. The XGBoost and LR models together confirm that age, admission FMA-LE, admission FAC, and lower extremity spasticity are the key factors influencing independent walking in stroke patients at hospital discharge. TRIAL REGISTRATION: Not applicable.
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Aprendizado de Máquina , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Caminhada , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/diagnóstico , Idoso , Caminhada/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Máquina de Vetores de Suporte , Prognóstico , Valor Preditivo dos Testes , AdultoRESUMO
Bacterial endotoxin lipopolysaccharide (LPS)-induced inflammatory response and ferroptosis play an important role in urinary tract infections. Tolterodine has been used as a urinary tract antispasmodic and anticholinergic agent. However, the effects of Tolterodine against LPS-induced insults in human bladder epithelial cells (hBECs) have not been reported before. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays to determine the cell viability, reactive oxygen species (ROS) and malondialdehyde level detection were used to determine the level of oxidative stress, enzyme-linked immunosorbent assay and Western blot analysis were used to detect the protein level. In the current study, we found that Tolterodine ameliorated LPS-induced production of ROS and lipid oxidation in hBECs. Interestingly, Tolterodine inhibited the production of interleukin 6, interleukin-1ß, and tumor necrosis factor α. Also, Tolterodine reduced the levels of Fe2+ and suppressed ferroptosis by reducing the levels of glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2, and acyl-CoA synthetase long-chain family member 4 in LPS-challenged bladder epithelial cells. Mechanistically, it was shown that Tolterodine restored the nuclear factor E2-related factor 2 (Nrf2)/nuclear factor-κB signaling. Importantly, inhibition of Nrf2 with its specific inhibitor ML385 abolished the protective effects of Tolterodine in the inflammatory response and ferroptosis, suggesting that the effects of Tolterodine are mediated by Nrf2. Based on these findings, we conclude that Tolterodine might serve as a promising agent for the treatment of LPS-induced bladder inflammation.
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Ferroptose , Lipopolissacarídeos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Lipopolissacarídeos/toxicidade , Tartarato de Tolterodina , Fator 2 Relacionado a NF-E2/metabolismo , Bexiga Urinária/metabolismo , Células Epiteliais/metabolismoRESUMO
KEY MESSAGE: Two peanut LEC1-type genes exhibit partial functional redundancy. AhNFYB10 could complement almost all the defective phenotypes of lec1-2 in terms of embryonic morphology, while AhNF-YB1 could partially affect these phenotypes. LEAFY COTYLEDON1 (LEC1) is a member of the nuclear factor Y (NF-Y) family of transcription factors and has been identified as a key regulator of embryonic development. In the present study, two LEC1-type genes from Arachis hypogeae were identified and designated as AhNF-YB1 and AhNF-YB10; these genes belong to subgenome A and subgenome B, respectively. The functions of AhNF-YB1 and AhNF-YB10 were investigated by complementation analysis of their defective phenotypes of the Arabidopsis lec1-2 mutant and by ectopic expression in wild-type Arabidopsis. The results indicated that both AhNF-YB1 and AhNF-YB10 participate in regulating embryogenesis, embryo development, and reserve deposition in cotyledons and that they have partial functional redundancy. In contrast, AhNF-YB10 complemented almost all the defective phenotypes of lec1-2 in terms of embryonic morphology and hypocotyl length, while AhNF-YB1 had only a partial effect. In addition, 30-40% of the seeds of the AhNF-YB1 transformants exhibited a decreasing germination ratio and longevity. Therefore, appropriate spatiotemporal expression of these genes is necessary for embryo morphogenesis at the early development stage and is responsible for seed maturation at the mid-late development stage. On the other hand, overexpression of AhNF-YB1 or AhNF-YB10 at the middle to late stages of Arabidopsis seed development improved the weight, oil content, and fatty acid composition of the transgenic seeds. Moreover, the expression levels of several genes associated with fatty acid synthesis and embryogenesis were significantly greater in developing AhNF-YB10-overexpressing seeds than in control seeds. This study provides a theoretical basis for breeding oilseed crops with high yields and high oil content.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arachis/genética , Arachis/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Melhoramento Vegetal , Ácidos Graxos/metabolismo , Desenvolvimento Embrionário , Lipídeos , Sementes/metabolismoRESUMO
BACKGROUND: Construction of the nasal tip strut is an important part of rhinoplasty; the incidence of postoperative complications is closely related to the type of graft and the approach to cartilaginous framework construction. OBJECTIVES: To introduce a supplementary graft to support the cartilaginous framework. METHODS: Forty patients (37 female and 3 male), aged from 18 to 40 years (average 29), received a rhinoplasty using a spacer graft. Of these, 12 were primary cases and the other 28 had a previous rhinoplasty procedure. Postoperatively, all patients were photographed and asked to complete a satisfaction survey. Complications were collected retrospectively. RESULTS: Postoperatively, the mean nasofrontal angle was 141.92±1.26 degrees for the primary cases and 140.75±2.22 degrees for the repeat procedures; the mean nasolabial angle was 88.69±0.95 degrees for primary cases and 89.14±0.93 degrees for the repeat procedures; mean nasal length was 4.78±0.05 cm for primary cases and 4.79±0.07 cm for the repeat procedures; mean tip projection was 4.68±6.35 cm for primary cases and 2.24±0.07 cm for the repeat procedures. Self-report of the overall improvements showed a high satisfaction rate. One case (2.5%) had a postoperative complication involving a mildly deviated columellar. CONCLUSIONS: The spacer graft can be used as an effective supplement to the traditional methods for reconstructing the nasal tip framework; it can prevent the occurrence of postoperative complications such as the exposure of the nasal prosthesis, the downward rotation of the nasal tip, the depression of the supratip regions of the nose, and the deviation of the nasal columella.
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Satisfação do Paciente , Rinoplastia , Humanos , Rinoplastia/métodos , Feminino , Adulto , Masculino , Adolescente , Estudos Retrospectivos , Complicações Pós-Operatórias , Resultado do Tratamento , Adulto Jovem , Cartilagens Nasais/cirurgia , Cartilagens Nasais/transplante , Reoperação , Cartilagem/transplante , Nariz/cirurgiaRESUMO
PURPOSE: There are two main surgical fixation methods for the posterior malleolar fractures (PMFs), the anterior-to-posterior (AP) screws or via the posterolateral (PL) approach utilizing a buttress plate. This review aims to compare the clinical outcome between the AP screw fixation and the PL plate fixation for treating PMFs. METHODS: We searched all relevant publications about PMFs treated with AP screws or PL plates through electronic databases including the PubMed, the Cochrane Library, the Embase, the Wiley online library and the Web of Science. The meta-analysis was conducted to evaluated clinical outcomes including reduction quality, post-operative function and complications. RESULTS: Six studies (one single randomized controlled trial and five retrospective cohort studies) were enrolled. 172 patients underwent AP screw fixation and 214 patients underwent PL plate fixation with a total of 386 patients (169 males and 217 females). The PL plating group yielded better AOFAS scores(MD = 6.97, 95 % CI=[4.68, 9.27], Pï¼0.00001, I2 =0 %) and was more likely to achieve excellent anatomical reduction(OR=5.49, 95 % CI=[1.06, 28.42], P = 0.04, I2 =80 %). No differences were found in the bad reduction quality, incidences of complications (arthritis, neuralgia, superficial wound healing problems and implant failure), the walking VAS scores and the dorsiflexion restriction degrees. CONCLUSION: We suggest that the PL plate fixation method has the clinical benefit of achieving anatomical reduction and better AOFAS scores over the AP screw fixation for treating PMFs. No differences were found in the incidences of complications ( arthritis, neuralgia, superficial wound healing problems and implant failure), the walking VAS scores and the dorsiflexion restriction degrees. The posterior approach and the direct reduction are recommended for the treatment of the PMFs. LEVEL OF CONFIDENCE: â ¡b.
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Fraturas do Tornozelo , Placas Ósseas , Parafusos Ósseos , Fixação Interna de Fraturas , Humanos , Fraturas do Tornozelo/cirurgia , Placas Ósseas/efeitos adversos , Parafusos Ósseos/efeitos adversos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodosRESUMO
Realizing a highly efficient oxygen evolution reaction (OER) process is of great significance for hydrogen energy development. The main challenge still lies in fabricating superior electrocatalysts with favorable performance. Constructing electrocatalysts with ingenious lattice modifications is a considerable way for the rational design of highly active catalytic centers. Here, theoretical calculations predict that the lattice incorporation of Se atoms can effectively enhance the reaction activity of OER with a decreased energy barrier for the rate-determining step. To obtain the corresponding desired electrocatalyst, the optimized lattice Se-modified CoOOH, with the ideal OER performance of low overpotential and stability, was delicately designed and fabricated by the electrochemical activation of the Co0.85Se precatalyst. X-ray absorption spectroscopy (XAS) demonstrates that lattice incorporation is more likely to be generated in Co0.85Se compared to CoSe2 and CoO precatalysts, which promoted the subsequent OER process. This work clarified the correlation between the precatalyst and the lattice-modified final catalyst in connection with electrochemical reconstruction.
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Parkinson's disease (PD) is the second most common neurodegenerative disease. Several single gene mutations involved in PD have been identified such as leucine-rich repeat kinase 2 (LRRK2), the most common cause of sporadic and familial PD. Its mutations have attracted much attention to therapeutically targeting this kinase. To date, many compounds including small chemical molecules with diverse scaffolds and RNA agents have been developed with significant amelioration in preclinical PD models. Currently, five candidates, DNL201, DNL151, WXWH0226, NEU-723 and BIIB094, have advanced to clinical trials for PD treatment. In this review, we describe the structure, pathogenic mutations and the mechanism of LRRK2, and summarize the development of LRRK2 inhibitors in preclinical and clinical studies, trying to provide an insight into targeting LRRK2 for PD intervention in future.
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Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Leucina , Proteínas Serina-Treonina Quinases/genética , MutaçãoRESUMO
BACKGROUND: Accurate segmentation of neonatal brain tissues and structures is crucial for studying normal development and diagnosing early neurodevelopmental disorders. However, there is a lack of an end-to-end pipeline for automated segmentation and imaging analysis of the normal and abnormal neonatal brain. OBJECTIVE: To develop and validate a deep learning-based pipeline for neonatal brain segmentation and analysis of structural magnetic resonance images (MRI). MATERIALS AND METHODS: Two cohorts were enrolled in the study, including cohort 1 (582 neonates from the developing Human Connectome Project) and cohort 2 (37 neonates imaged using a 3.0-tesla MRI scanner in our hospital).We developed a deep leaning-based architecture capable of brain segmentation into 9 tissues and 87 structures. Then, extensive validations were performed for accuracy, effectiveness, robustness and generality of the pipeline. Furthermore, regional volume and cortical surface estimation were measured through in-house bash script implemented in FSL (Oxford Centre for Functional MRI of the Brain Software Library) to ensure reliability of the pipeline. Dice similarity score (DSC), the 95th percentile Hausdorff distance (H95) and intraclass correlation coefficient (ICC) were calculated to assess the quality of our pipeline. Finally, we finetuned and validated our pipeline on 2-dimensional thick-slice MRI in cohorts 1 and 2. RESULTS: The deep learning-based model showed excellent performance for neonatal brain tissue and structural segmentation, with the best DSC and the 95th percentile Hausdorff distance (H95) of 0.96 and 0.99 mm, respectively. In terms of regional volume and cortical surface analysis, our model showed good agreement with ground truth. The ICC values for the regional volume were all above 0.80. Considering the thick-slice image pipeline, the same trend was observed for brain segmentation and analysis. The best DSC and H95 were 0.92 and 3.00 mm, respectively. The regional volumes and surface curvature had ICC values just below 0.80. CONCLUSIONS: We propose an automatic, accurate, stable and reliable pipeline for neonatal brain segmentation and analysis from thin and thick structural MRI. The external validation showed very good reproducibility of the pipeline.
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Aprendizado Profundo , Recém-Nascido , Humanos , Reprodutibilidade dos Testes , Neuroimagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodosRESUMO
Objective: To analyze the effects of sodium hyaluronate administration on the serum levels of antioxidase, substance P (SP), and neuropeptide Y (NPY) in patients undergoing locking plate fixation (LPF) for tibial plateau fractures (TPF). Methods: We retrospectively analyzed the records of 66 patients with TPF who received treatment in the Beijing Chao-yang Hospital[PJMS1][2] from February 2017 to August 2020. According to the treatment records, 33 patients underwent LPF surgery (control-group), and 33 patients underwent LPF plus sodium hyaluronate treatment (observation-group). The levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (TAC)), SP and NPY. Results: Seven days after LPF operations, both groups showed lower levels of SOD, CAT, and TAC compared to pre-surgery levels, while levels of SP and NPY were higher. However, the observation group showed higher levels of SOD, CAT, and TAC compared to the control group, and lower levels of SP and NPY in the control group (P<0.05). Conclusion: The treatment of TPF with LPF plus sodium hyaluronate administration has been shown to effectively reduce oxidative stress reactions, improve SP and NPY levels.[PJMS3][4].
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OBJECTIVE: To explore whether magnetic susceptibility value (MSV) and radiomics features of the nigrostriatal system could be used as imaging markers for diagnosing Parkinson's disease (PD) and its related cognitive impairment (CI). METHODS: A total of 104 PD patients and 45 age-sex-matched healthy controls (HCs) underwent quantitative susceptibility mapping (QSM). The former completed Hoehn-Yahr Stage and Montreal Cognitive Assessment (MoCA). The patients were divided into several subgroups according to disease stages, courses, and MoCA scores. The ROI was subdivided into the substantia nigra (SN), head of caudate nucleus (HCN), and putamen. The MSVs and radiomics features were obtained from QSM. The multivariable logistic regression (MLR) and support vector machine (SVM) models were constructed to diagnose PD. The correlations between MSVs, radiomics features, and MoCA scores were evaluated. RESULTS: The MSVs in bilateral SN pars compacta (SNc) of PD patients were higher than those of the HCs (p < 0.001). There were differences in some radiomics features between the two groups (p < 0.05). The MSVs of the right SNc and the radiomics features of the right SN had the highest area under the curve (AUC), respectively. The comprehensive MLR model (0.90) and SVM model (0.95) revealed better classification performance than MSVs (p < 0.05) in diagnosing PD. The MSVs from the HCN were negatively correlated with MoCA scores in PD subgroups. There were correlations between radiomics features and MoCA scores in PD patients. CONCLUSIONS: Radiomics features and MSVs of the nigrostriatal system from QSM could have crucial role in diagnosing PD and assessing CI. KEY POINTS: ⢠The MLR and the SVM models have excellent diagnostic performance in the diagnosis of PD. ⢠A PD diagnostic nomogram, created based on MSV and the radiomics scores of SVM model, is very convenient for clinical use. ⢠The radiomics features of the nigrostriatal system based on QSM help to evaluate the cognitive impairment in PD patients.
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Disfunção Cognitiva , Doença de Parkinson , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Ferro , Imageamento por Ressonância Magnética/métodos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Substância NegraRESUMO
Arsenic doping in silicides has been much less studied compared with phosphorus. In this study, superconductivity is successfully induced by As doping in Mo5Si3. The superconducting transition temperature (Tc) reaches 7.7 K, which is higher than those in previously known W5Si3-type superconductors. Mo5Si2As is a type-II BCS superconductor with upper and lower critical fields of 6.65 T and 22.4 mT, respectively. In addition, As atoms are found to selectively take the 8h sites in Mo5Si2As. The emergence of superconductivity is possibly due to the shift of Fermi level as a consequence of As doping, as revealed by the specific heat measurements and first-principles calculations. Our work provides not only another example of As doping but also a practical strategy to achieve superconductivity in silicides through Fermi level engineering.
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PURPOSE: The injury mechanisms and classifications of tibial plateau fractures (TPFs) are still controversial. The aim of this study is to show 3D fracture mapping of different types of tibial plateau fractures. Moreover, combined with Schatzker and ten-segment classification, we aimed to analyze the injury frequency and characteristics of different segments. METHODS: In total, 346 patients with TPFs treated at level I trauma centres from 2017 to 2021 were reviewed. The CT files of the included cases were typed and categorized. 3D reconstruction of TPFs patients' CT files were performed using software. All fracture lines were superimposed on the standard model by the software to create TPFs 3D fracture mapping. RESULTS: This study included 204 male and 142 female patients (average age, 47 years [range, 18 to 83 years]) with a tibial plateau fracture. Using the Schatzker classification, we found 39 type I (11.27%), 103 type II (29.77%), nine type III (2.60%), 71 type IV (20.52%), 52 type V (15.03%), 59 type VI (17.05%) fractures, and 13 others (3.76%). The density areas of fracture lines are mainly located in the ALC and PLC segments (74.3%, 69.1%). In different views, fracture lines of different Schatzker types showed distinct distribution characteristics. CONCLUSIONS: Schatzker classification combined with 3D fracture mapping provides a new presentation of tibial plateau fracture morphology. According to the 3D fracture mapping, different types of TPFs have distinctly different distribution characteristics of fracture lines. There are significant differences between different types of fracture injury segments.
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Fraturas da Tíbia , Tomografia Computadorizada por Raios X , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Software , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Tomografia Computadorizada por Raios X/métodos , Centros de TraumatologiaRESUMO
Circular RNAs (circRNAs) are important players in prostate cancer (PCa) development and progression, but their detailed mechanisms have not been elucidated. Herein, hsa_circ_0007494 was suppressed in the PCa cell lines and tissues. This resulted in metastasis of tumors to the lymph node and predicted tumor stage. Functionally, overexpression of hsa_circ_0007494 inhibited the proliferation and invasive capacity of the cells in vitro and blocked the growth of tumors in vivo. Hsa_circ_0007494 functioned as a "molecular sponge" for miR-616 and hence upregulated the target of miR-616, PTEN. In addition, rescue assays revealed that PTEN silencing (or miR-616 mimics) blocked the tumor-suppressing effects of hsa_circ_0007494 overexpression on PCa progression. Together, our findings indicate that hsa_circ_0007494 suppresses PCa by forming a negative regulatory network including hsa_circ_0007494/miR-616/PTEN. Thus, hsa_circ_0007494 may be a treatment target for PCa.
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Proliferação de Células/fisiologia , Genes Supressores de Tumor/fisiologia , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Próstata/metabolismo , Apoptose/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
We report a detailed study of tunneling spectra measured on 2H-Ta_{x}Nb_{1-x}Se_{2} (x=0â¼0.1) single crystals using a low-temperature scanning tunneling microscope. The prominent gaplike feature, which has not been understood for a long time, was found to be accompanied by some "in-gap" fine structures. By investigating the second-derivative spectra and their temperature and magnetic field dependencies, we were able to prove that inelastic electron tunneling is the origin of these features and obtain the Eliashberg function of 2H-Ta_{x}Nb_{1-x}Se_{2} at an atomic scale, providing a potential way to study the local Eliashberg function and the phonon spectra of the related transition-metal dichalcogenides.
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Because the transcription factor activator protein-1 (AP-1) regulates a variety of protein-encoding genes, it is a participant in many cellular functions, including proliferation, transformation, epithelial mesenchymal transition (EMT), and apoptosis. Inhibitors targeting AP-1 have potential use in the treatment of cancer and other inflammatory diseases. Here, we identify veratramine as a potent natural modulator of AP-1, which selectively binds to a specific site (TRE 5'-TGACTCA-3') of the AP-1 target DNA sequence and regulates AP-1-dependent gene transcription without interfering with cystosolic signaling cascades that might lead to AP-1 activation. Moreover, RNA-seq experiments demonstrate that veratramine does not act on the Hedgehog signaling pathway in contrast to its analogue, cyclopamine, and likely does not harbor the same teratogenicity and toxicity. Additionally, veratramine effectively suppresses EGF-induced AP-1 transactivation and transformation of JB6 P+ cells. Finally, we demonstrate that veratramine inhibits solar-ultraviolet-induced AP-1 activation in mice. The identification of veratramine and new findings in its specific regulation of AP-1 down stream genes pave ways to discovering and designing regulators to regulate transcription factor.
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DNA/metabolismo , Fator de Transcrição AP-1/metabolismo , Ativação Transcricional/efeitos dos fármacos , Alcaloides de Veratrum/farmacologia , Animais , Sequência de Bases , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/efeitos da radiação , DNA/genética , Perfilação da Expressão Gênica , Células HeLa , Humanos , Camundongos , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Fator de Transcrição AP-1/genética , Ativação Transcricional/efeitos da radiação , Raios UltravioletaRESUMO
Phenotypic convergence between distantly related taxa often mirrors adaptation to similar selective pressures and may be driven by genetic convergence. The giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens) belong to different families in the order Carnivora, but both have evolved a specialized bamboo diet and adaptive pseudothumb, representing a classic model of convergent evolution. However, the genetic bases of these morphological and physiological convergences remain unknown. Through de novo sequencing the red panda genome and improving the giant panda genome assembly with added data, we identified genomic signatures of convergent evolution. Limb development genes DYNC2H1 and PCNT have undergone adaptive convergence and may be important candidate genes for pseudothumb development. As evolutionary responses to a bamboo diet, adaptive convergence has occurred in genes involved in the digestion and utilization of bamboo nutrients such as essential amino acids, fatty acids, and vitamins. Similarly, the umami taste receptor gene TAS1R1 has been pseudogenized in both pandas. These findings offer insights into genetic convergence mechanisms underlying phenotypic convergence and adaptation to a specialized bamboo diet.
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Ailuridae/genética , Evolução Biológica , Genoma , Ursidae/genética , Adaptação Fisiológica , Ailuridae/classificação , Animais , Bambusa/química , Digestão/genética , Comportamento Alimentar , Herbivoria/genética , Mamíferos/classificação , Mamíferos/genética , Fenótipo , Filogenia , Pseudogenes , Receptores Acoplados a Proteínas G/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Papilas Gustativas , Dedos do Pé/anatomia & histologia , Dedos do Pé/fisiologia , Ursidae/classificaçãoRESUMO
PURPOSE: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. The toughest issue traumatic orthopaedic surgeons are faced with is how to maintain a balance between adequate COVID-19 screening and timely surgery. In this study, we described our experience with pre-operative COVID-19 screening in patients with traumatic fractures. Furthermore, we analysed the clinical results of fracture patients undergoing confined or emergency surgery during the COVID-19 outbreak. METHODS: This was a case series study. Patients with traumatic fractures who were admitted to our hospital for surgery were enrolled in this study during the COVID-19 outbreak from March to April 2020. All patients were enrolled and managed using the standardized clinical pathway we designed for preoperative COVID-19 screening. Clinical, laboratory and outcome data were analysed. RESULTS: The average surgery waiting time from injury to surgery was 8.7 ± 3.4 days. The average waiting time from admission to surgery was 5.3 ± 2.8 days. These average waiting times were increased by 4.1 days and 2.0 days, respectively, compared with 2019 data. Cardiovascular complications, venous thromboembolism and pneumonia occurred in one, two and one patient, respectively. Three and two patients developed pre-operative and postoperative fevers, respectively. CONCLUSIONS: We introduced a novel clinical pathway for pre-operatively screening of COVID-19 in traumatic orthopaedic patients. The delay in surgery caused by COVID-19 screening was minimized to a point at which reasonable and acceptable clinical outcomes were achieved. Doctors should pay more attention to perioperative complications, such as cardiovascular complications, venous thromboembolism, pneumonia and fever.