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1.
Materials (Basel) ; 17(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38730900

RESUMO

This study investigates the mechanical properties of titanium carbide/aluminum metal matrix composites (AMMCs) using both experimental and computational methods. Through accumulative roll bonding (ARB) and cryorolling (CR) processes, AA1050 alloy surfaces were reinforced with TiCp particles to create the Al-TiCp composite. The experimental analysis shows significant improvements in tensile strength, yield strength, elastic modulus, and hardness. The finite element analysis (FEA) simulations, particularly the microstructural modeling of RVE-1 (the experimental case model), align closely with the experimental results observed through scanning electron microscopy (SEM). This validation underscores the accuracy of the computational models in predicting the mechanical behavior under identical experimental conditions. The simulated elastic modulus deviates by 5.49% from the experimental value, while the tensile strength shows a 6.81% difference. Additionally, the simulated yield strength indicates a 2.85% deviation. The simulation data provide insights into the microstructural behavior, stress distribution, and particle-matrix interactions, facilitating the design optimization for enhanced performance. The study also explores the influence of particle shapes and sizes through Representative Volume Element (RVE) models, highlighting nuanced effects on stress-strain behavior. The microstructural evolution is examined via transmission electron microscopy (TEM), revealing insights regarding grain refinement. These findings demonstrate the potential of Al-TiCp composites for lightweight applications.

2.
ACS Appl Mater Interfaces ; 16(19): 24601-24611, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38710043

RESUMO

The Zn dendrite growth and side reactions are two major issues for the practical use of Zn metal anodes (ZMAs). Herein, an N-doped carbon-based hybrid fiber with the 3D porous skeleton and the zincophilic Cu nanoparticles (denoted as Cu@HLCF) is developed for stable ZMAs. The zincophilic Cu particles in the skeleton work as the active sites to facilitate uniform Zn nucleation. Meanwhile, the abundant pores in the framework of the hybrid fibers provide a large space to relieve the structural stress and suppress the dendrite growth. Moreover, the good mechanical characteristics of the hybrid fiber ensure its high potential applications for flexible electronics. Theoretical analysis results disclose the strong interaction between Zn and Cu sites, and experimental results demonstrate the low voltage hysteresis, high reversibility, and dendrite-free behavior of the Cu@HLCF host for Zn plating/stripping. Moreover, the solid-state Zn-ion battery (ZIB) assembled with a Cu@HLCF/Zn anode shows the prominent flexibility, impressively reliability, and outstanding cycling capability. Therefore, this work not only provides a novel design for the efficient and stable Zn metal anode but also promotes the development of flexible power sources for flexible electronics.

3.
Front Neurosci ; 18: 1367932, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660227

RESUMO

Steady-state visual evoked potential brain-computer interfaces (SSVEP-BCI) have attracted significant attention due to their ease of deployment and high performance in terms of information transfer rate (ITR) and accuracy, making them a promising candidate for integration with consumer electronics devices. However, as SSVEP characteristics are directly associated with visual stimulus attributes, the influence of stereoscopic vision on SSVEP as a critical visual attribute has yet to be fully explored. Meanwhile, the promising combination of virtual reality (VR) devices and BCI applications is hampered by the significant disparity between VR environments and traditional 2D displays. This is not only due to the fact that screen-based SSVEP generally operates under static, stable conditions with simple and unvaried visual stimuli but also because conventional luminance-modulated stimuli can quickly induce visual fatigue. This study attempts to address these research gaps by designing SSVEP paradigms with stereo-related attributes and conducting a comparative analysis with the traditional 2D planar paradigm under the same VR environment. This study proposed two new paradigms: the 3D paradigm and the 3D-Blink paradigm. The 3D paradigm induces SSVEP by modulating the luminance of spherical targets, while the 3D-Blink paradigm employs modulation of the spheres' opacity instead. The results of offline 4-object selection experiments showed that the accuracy of 3D and 2D paradigm was 85.67 and 86.17% with canonical correlation analysis (CCA) and 86.17 and 91.73% with filter bank canonical correlation analysis (FBCCA), which is consistent with the reduction in the signal-to-noise ratio (SNR) of SSVEP harmonics for the 3D paradigm observed in the frequency-domain analysis. The 3D-Blink paradigm achieved 75.00% of detection accuracy and 27.02 bits/min of ITR with 0.8 seconds of stimulus time and task-related component analysis (TRCA) algorithm, demonstrating its effectiveness. These findings demonstrate that the 3D and 3D-Blink paradigms supported by VR can achieve improved user comfort and satisfactory performance, while further algorithmic optimization and feature analysis are required for the stereo-related paradigms. In conclusion, this study contributes to a deeper understanding of the impact of binocular stereoscopic vision mechanisms on SSVEP paradigms and promotes the application of SSVEP-BCI in diverse VR environments.

4.
Materials (Basel) ; 17(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38591395

RESUMO

In this study, AA1050/AA6061 laminated composites were prepared by three-cycle accumulative roll bonding (ARB) and subsequent rolling. The effects of the rolling process on the microstructure evolution and mechanical properties of AA1050/AA6061 laminated composites were systematically investigated. The results indicate that the mechanical properties of the laminated composites can be effectively improved by cryorolling compared with room-temperature rolling. The microstructure analysis reveals that cryorolling can suppress the necking of the hard layer to obtain a flat lamellar structure. Moreover, the microstructure characterized by transmission electron microscopy shows that cryorolling can inhibit the dynamic recovery and significantly refine the grain size of the constituent layers. Meanwhile, the tensile fracture surface illustrates that AA1050/AA6061 laminated composites have the optimal interfacial bonding quality after cryorolling. Therefore, the laminated composites obtain excellent mechanical properties with the contribution of these factors.

5.
Int J Biol Macromol ; 265(Pt 1): 130791, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479666

RESUMO

The combination of straw returning and nitrogen (N) fertilization is a popular tillage mode and essential strategy for achieving stable yield and high quality. However, the optimal combination strategy and the influence of tillage mode on the morphological, crystalline, and molecular structures of maize starch remain unclear. We conducted a long-term field experiment over 7 years in Northeast China using two tillage modes, rotary tillage with straw returning (RTS) and plow tillage with straw returning (PTS), and four N application rates. The relative crystallinity, 1045/1022 cm-1 value, and B2 and B3 chains of maize starch were higher under RTS than under PTS, resulting in increased stability of starch and improvements in gelatinization enthalpy and temperature. The surface of the starch granules induced by N fertilizer was smoother than that under the N0 (0 kg N ha-1) treatment. The proportion of amylose content, solubility, swelling power, and light transmittance increased under N2 (262 kg N ha-1) treatment, along with improvement in starch pasting properties. These results suggest that RTS combined with N2 treatment can regulate the morphological, structural, and physicochemical characteristics of maize starch, providing an essential reference for improving the quality of maize starch from an agronomic point of view.


Assuntos
Nitrogênio , Zea mays , Nitrogênio/análise , Agricultura/métodos , Amido/química , China , Fertilização , Solo/química
7.
J Neurointerv Surg ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503511

RESUMO

BACKGROUND: Data concerning restenosis following successful recanalization of non-acute internal carotid artery occlusion (ICAO) are scarce. This study was conducted to identify the incidence and predictors of restenosis following successful recanalization of non-acute ICAO. METHODS: We reviewed the incidence of restenosis (defined as >70% restenosis or reocclusion) among 252 consecutive patients with successful recanalization of non-acute ICAO. Baseline, imaging, and surgery-related characteristics were analyzed to assess their association with restenosis. A scoring system was developed to identify high-risk patients for restenosis. RESULTS: During a median follow-up of 12.6 months, restenosis occurred in 56 patients (22.2%), including 39 with reocclusion and 17 with >70% restenosis. The cumulative restenosis rate was 18.0% at 12 months and 24.1% at 24 months. The incidence of stroke was higher in patients with restenosis (25.0% vs 1.5%, P<0.01). Multivariate analysis showed occlusion length (5-10 cm vs <5 cm (hazard ratio (HR) 3.15, 95% confidence interval (95% CI) 1.07 to 9.29); ≥ 10 cm vs <5 cm (HR 5.01, 95% CI 1.73 to 14.49)), residual stenosis ≥30% (HR 3.08, 95% CI 1.79 to 5.30), and internal carotid artery (ICA) wall collapse (HR 1.96, 95% CI 1.12 to 3.44) as independent predictors of restenosis. Point scores proportional to model coefficients were assigned, with scores ranging from 0 to 6. Patients scoring 3-6 had a 4.00 times higher chance of developing restenosis (95% CI 2.35 to 6.79) compared with those scoring 0-2. CONCLUSIONS: Nearly one in five patients experienced restenosis following successful recanalization of non-acute ICAO. Occlusion length, residual stenosis ≥30%, and ICA wall collapse were independently associated with restenosis.

8.
Nat Commun ; 15(1): 2163, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461299

RESUMO

Recent development of new immune checkpoint inhibitors has been particularly successfully in cancer treatment, but still the majority patients fail to benefit. Converting resistant tumors to immunotherapy sensitive will provide a significant improvement in patient outcome. Here we identify Mi-2ß as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response. Studies in genetically engineered mouse melanoma models indicate that loss of Mi-2ß rescues the immune response to immunotherapy in vivo. Mechanistically, ATAC-seq analysis shows that Mi-2ß controls the accessibility of IFN-γ-stimulated genes (ISGs). Mi-2ß binds to EZH2 and promotes K510 methylation of EZH2, subsequently activating the trimethylation of H3K27 to inhibit the transcription of ISGs. Finally, we develop an Mi-2ß-targeted inhibitor, Z36-MP5, which reduces Mi-2ß ATPase activity and reactivates ISG transcription. Consequently, Z36-MP5 induces a response to immune checkpoint inhibitors in otherwise resistant melanoma models. Our work provides a potential therapeutic strategy to convert immunotherapy resistant melanomas to sensitive ones.


Assuntos
DNA Helicases , Proteína Potenciadora do Homólogo 2 de Zeste , Evasão da Resposta Imune , Melanoma , Animais , Humanos , Camundongos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Evasão da Resposta Imune/genética , Melanoma/tratamento farmacológico , Metilação , DNA Helicases/genética , DNA Helicases/metabolismo
9.
J Histochem Cytochem ; 72(2): 95-108, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213081

RESUMO

This study aimed to evaluate the effects of general control non-derepressible 2 (GCN2) on osteoarthritis (OA) in vivo and in vitro. First, anterior cruciate ligament transection (ACLT)-induced rat model and interleukin (IL)-1ß-induced ATDC5 chondrocyte were established. Hematoxylin and eosin staining and safranin O/fast green staining were employed for analyzing the histological changes in the rat cartilage. In addition, immunohistochemistry, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blot, and immunofluorescence staining were employed for examining cartilage degeneration-, inflammation-, autophagy-, and NLR family pyrin domain containing 3 (NLRP3) inflammasome-associated genes expression. Moreover, 2,7-dichlorodihydrofluorescein acetoacetic acid probe was utilized for examining the intracellular reactive oxygen species. In addition, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were applied for detecting chondrocyte proliferation and apoptosis IL-1ß-treated ATDC5 chondrocytes. GCN2 overexpression ameliorated articular cartilage degeneration and inflammation but promoted chondrocyte autophagy in ACLT-induced OA rats. Similarly, we demonstrated that the upregulation of GCN2 could promote chondrocyte proliferation, suppress chondrocyte apoptosis, attenuate chondrocyte inflammation and extracellular matrix degradation, and promote chondrocyte autophagy. Moreover, GCN2 overexpression could inhibit the activation of NLRP3 inflammasome in IL-1ß-induced ATDC5 chondrocyte. Furthermore, 3-methyladenine neutralized the protective and autophagy-promoting effects of GCN2 overexpression on ATDC5 chondrocytes. GCN2 could attenuate inflammation and cartilage degeneration, promote chondrocyte autophagy, and inhibit NLRP3 inflammasome activation in OA.


Assuntos
Cartilagem Articular , Osteoartrite , Ratos , Animais , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Inflamação/patologia , Apoptose , Condrócitos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia
10.
Neurosurg Rev ; 47(1): 25, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163848

RESUMO

The role of superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass in acute ischemic stroke (AIS) is contentious, with no evidence in patients with AIS and large vessel occlusion (AIS-LVO). We conducted a cohort study to assess emergency STA-MCA outcomes in AIS-LVO and a meta-analysis to evaluate STA-MCA outcomes in early AIS treatment. From January 2018 to March 2021, we consecutively recruited newly diagnosed AIS-LVO patients, dividing them into STA-MCA and non-STA-MCA groups. To evaluate the neurological status and outcomes, we employed the National Institutes of Health Stroke Scale (NIHSS) during the acute phase and the modified Rankin Scale (mRS) during the follow-up period. Additionally, we conducted a meta-analysis encompassing all available clinical studies to assess the impact of STA-MCA on patients with AIS. In the cohort study (56 patients), we observed more significant neurological improvement in the STA-MCA group at two weeks (p = 0.030). However, there was no difference in the clinical outcomes between the two groups. Multivariable logistic regression identified the NIHSS at two weeks (OR: 0.840; 95% CI: 0.754-0.936, p = 0.002) as the most critical predictor of a good outcome. Our meta-analysis of seven studies indicated a 67% rate for achieving a good outcome (mRS < 3) at follow-up points (95% CI: 57%-77%, I2 = 44.1%). In summary, while the meta-analysis suggested the potential role of STA-MCA bypass in mild to moderate AIS, our single-center cohort study indicated that STA-MCA bypass does not seem to improve the prognosis of patients who suffer from AIS-LVO.


Assuntos
Revascularização Cerebral , AVC Isquêmico , Acidente Vascular Cerebral , Doenças Vasculares , Humanos , Artéria Cerebral Média/cirurgia , Estudos de Coortes , Artérias Temporais/cirurgia , Acidente Vascular Cerebral/cirurgia , Estudos Retrospectivos
11.
Heliyon ; 10(1): e23539, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38223714

RESUMO

Tourism motivation and satisfaction are classic themes in tourism research. This study combines latent Dirichlet allocation (LDA) and the Censydiam motivation model to analyze online reviews of tourism in Qinghai, China. The aim of this research is to explore tourist motivation through online reviews and provide innovative service suggestions to improve tourist satisfaction. The LDA model initially extracts six main topics from online comments. Then, using the fuzzy analytic hierarchy process (FAHP), it maps the relationship between topics and tourism motivations to propose strategies for enhancing tourists' enjoyment, conviviality, and other motivating factors. Furthermore, we employ the Kano model to evaluate tourists' satisfaction levels regarding these strategies, demonstrating their positive evaluations. Hence, this study provides tourism industry professionals and service designers with an innovative method for understanding tourists' motivations through online reviews, enabling them to design specific services that enhance tourism experiences.

12.
Prep Biochem Biotechnol ; 54(3): 282-293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37395553

RESUMO

"Zicao" has a long medicinal history and has a variety of pharmacological activities. As the main resource of "zicao" in Tibet, Onosma glomeratum Y. L. Liu (tuan hua dian zi cao), usually used for treating pneumonia in Tibet, has not been reported deeply. In order to determine the main anti-inflammatory active ingredients of Onosma glomeratum Y. L. Liu, in this study, the extracts enriched in naphthoquinones and polysaccharides were optimized prepared form Onosma glomeratum Y. L. Liu by ultrasonic extraction, and reflux extraction, respectively, with Box-Behnken design effect surface method. And their anti-inflammatory abilities were screened on LPS induced A549 cells model, for figuring out the anti-inflammatory active ingredients from Onosma glomeratum Y. L. Liu.The extract enriched naphthoquinone was obtained under following condition: extract with 85% ethanol in a liquid to material ratio of 1:40 g/mL at 30 °C for 30 minutes using ultrasound, leading to the extraction rate of total naphthoquinone as 0.98 ± 0.017%; the extract enriched polysaccharides was prepared as follows: extract 82 minutes at 100 °C with distilled water in a liquid to material ratio of 1:50 g/mL, with extraction rate of polysaccharide as 7.07 ± 0.02%.On the LPS-induced A549 cell model, the polysaccharide extract from Onosma glomeratum Y. L. Liu showed better anti-inflammatory effects than the naphthoquinone extract, indicating the extract enriched in polysaccharides is the anti-inflammatory extract of Onosma glomeratum Y. L. Liu, which could serve as a potential anti-inflammatory extract in medical and food industries in the future.


Assuntos
Boraginaceae , Naftoquinonas , Lipopolissacarídeos , Anti-Inflamatórios/farmacologia , Polissacarídeos/farmacologia
13.
Hepatology ; 79(1): 118-134, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37594323

RESUMO

BACKGROUND AND AIM: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining "high-risk" have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. APPROACH AND RESULTS: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). CONCLUSIONS: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.


Assuntos
Varizes Esofágicas e Gástricas , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Varizes Esofágicas e Gástricas/etiologia , Prognóstico , Modelos Estatísticos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Cirrose Hepática/etiologia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos
14.
Med Res Rev ; 44(2): 686-706, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37983866

RESUMO

Cancer continues to be a major health concern globally, although the advent of targeted therapy has revolutionized treatment options. Aurora Kinase B is a serine-threonine kinase that has been explored as an oncology therapeutic target for more than two decades. Aurora Kinase B inhibitors show promising biological results in in-vitro and in-vivo experiments. However, there are no inhibitors approved yet for clinical use, primarily because of the side effects associated with Aurora B inhibitors. Several studies demonstrate that Aurora B inhibitors show excellent synergy with various chemotherapeutic agents, radiation therapy, and targeted therapies. This makes it an excellent choice as an adjuvant therapy to first-line therapies, which greatly improves the therapeutic window and side effect profile. Recent studies indicate the role of Aurora B in some deadly cancers with limited therapeutic options, like triple-negative breast cancer and glioblastoma. Herein, we review the latest developments in Aurora Kinase B targeted research, with emphasis on its potential as an adjuvant therapy and its role in some of the most difficult-to-treat cancers.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Aurora Quinase B/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/uso terapêutico , Neoplasias/tratamento farmacológico , Aurora Quinase A/uso terapêutico , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
15.
J Interv Med ; 6(3): 126-129, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37846337

RESUMO

Endovascular coil embolization is a minimally invasive, rapid, and effective method for the treatment of intracranial aneurysms. However, complications associated with coil embolization, such as intraoperative aneurysm rupture or arterial occlusion, should be promptly managed during the procedure to avoid catastrophic consequences. This study presents a case of mechanical compression management of the right middle cerebral artery (MCA) inferior trunk during coil embolization for bilateral MCA aneurysms. The inferior trunk of the right MCA was abruptly occluded due to mechanical compression during coil embolization of the right MCA bifurcation aneurysm. A Solitaire AB stent (4 â€‹× â€‹20 mm, Covidien/Medtronic, Dublin, Ireland) was implanted in the inferior trunk of the right MCA after tirofiban was injected via a microcatheter, and the right inferior trunk was recanalized. The patient also underwent coil embolization of the left MCA bifurcation aneurysm, without any complications. It is crucial to recognize compressive occlusion of adjacent aneurysm branches to avoid severe complications during intracranial aneurysm embolization. Stent placement is a rescue treatment option for recanalization of an occluded artery.

16.
Immunohorizons ; 7(9): 619-625, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37712913

RESUMO

Organ supply remains inadequate to meet the needs of many patients who could benefit from allotransplantation. Xenotransplantation, the use of animals as organ donors, provides an opportunity to alleviate this challenge. Pigs are widely accepted as the ideal organ donor, but humans and nonhuman primates have strong humoral immune responses to porcine tissue. Although carbohydrate xenoantigens have been studied intensively, the primate Ab response also targets class I and class II swine leukocyte Ags (SLAs). Human Abs that recognize HLAs can cross-react with SLA molecules because epitopes can be shared across species. However, ∼15% of people may also exhibit Abs toward class II SLAs despite lacking Abs that also recognize class II HLAs. Here, we extend these studies to better understand human Ab responses toward class I SLAs. When tested against a panel of 18 unique class I SLA proteins, 14 of 52 sera samples collected from patients in need of an organ transplant contained Abs that bound class I SLAs. Class I SLA-reactive sera may contain IgM only, IgG, only, or IgM and IgG capable of recognizing the pig proteins. The presence of class I HLA-reactive Abs was not essential to generating anti-class I SLA Ig. Last, anti-class I SLA reactivity varied by serum; some recognized a single SLA allele, whereas others recognized multiple class I SLA proteins.


Assuntos
Leucócitos , Listas de Espera , Humanos , Animais , Suínos , Imunoglobulina G , Imunoglobulina M
17.
Cell Metab ; 35(10): 1782-1798.e8, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37586363

RESUMO

Glucose metabolism is known to orchestrate oncogenesis. Whether glucose serves as a signaling molecule directly regulating oncoprotein activity for tumorigenesis remains elusive. Here, we report that glucose is a cofactor binding to methyltransferase NSUN2 at amino acid 1-28 to promote NSUN2 oligomerization and activation. NSUN2 activation maintains global m5C RNA methylation, including TREX2, and stabilizes TREX2 to restrict cytosolic dsDNA accumulation and cGAS/STING activation for promoting tumorigenesis and anti-PD-L1 immunotherapy resistance. An NSUN2 mutant defective in glucose binding or disrupting glucose/NSUN2 interaction abolishes NSUN2 activity and TREX2 induction leading to cGAS/STING activation for oncogenic suppression. Strikingly, genetic deletion of the glucose/NSUN2/TREX2 axis suppresses tumorigenesis and overcomes anti-PD-L1 immunotherapy resistance in those cold tumors through cGAS/STING activation to facilitate apoptosis and CD8+ T cell infiltration. Our study identifies NSUN2 as a direct glucose sensor whose activation by glucose drives tumorigenesis and immunotherapy resistance by maintaining TREX2 expression for cGAS/STING inactivation.


Assuntos
Nucleotidiltransferases , Transdução de Sinais , Humanos , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Transdução de Sinais/genética , Carcinogênese , Imunoterapia , Metiltransferases/metabolismo
18.
Sci Rep ; 13(1): 10999, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37419961

RESUMO

This study explored the relationship between femoral lateralization and femoral neck-shaft angle after intramedullary nail (IM) fixation for per trochanteric fractures. 70 patients (AO/OTA 31A1-2) were investigated. Anteroposterior (AP) and lateral X-ray views pre- and post-operation were recorded. Patients were classified into three groups according to the position of the medial cortex of the head-neck fragment to that of the femoral shaft: being slightly superomedial (positive medial cortex support, PMCS), being smoothly contacted (neutral position, NP) or being displaced laterally (negative medial cortex support, NMCS). Patient demographics, femoral lateralization, and neck-shaft angle were measured and statistically analyzed pre- and post-operation. Functional recovery was evaluated by Harris score 3- and 6- months post-operation. All cases ultimately demonstrated radiographic fracture union. There was a tendency to have an increased neck-shaft angle (valgus alignment) in the PMCS group and increased femoral lateralization in the NP group (p < 0.05). Among those three groups, the change in femoral lateralization and neck-shaft angle was statistically different (p < 0.05). An inverse relationship between femoral lateralization and femoral neck-shaft angle was observed. Femoral lateralization increased correspondingly when the neck-shaft angle continuously decreased from the PMCS group to the NP group and then to the NMCS group, and patients in the PMCS group had better functional recovery than the other two groups (p < 0.05). Femoral lateralization was commonly produced after IM fixation for per trochanteric fractures. The fracture fixed in PMCS mode possesses the slightest change in femoral lateralization while maintaining valgus alignment of the femoral neck-shaft angle and good functional outcome, which is superior to NP or NMCS mode.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Quadril , Humanos , Fixação Intramedular de Fraturas/efeitos adversos , Pinos Ortopédicos , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Fêmur/cirurgia , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
19.
Opt Express ; 31(10): 16781-16794, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37157750

RESUMO

Whispering gallery mode (WGM) resonators provide an important platform for fine measurement thanks to their small size, high sensitivity, and fast response time. Nevertheless, traditional methods focus on tracking single-mode changes for measurement, and a great deal of information from other resonances is ignored and wasted. Here, we demonstrate that the proposed multimode sensing contains more Fisher information than single mode tracking and has great potential to achieve better performance. Based on a microbubble resonator, a temperature detection system has been built to systematically investigate the proposed multimode sensing method. After the multimode spectral signals are collected by the automated experimental setup, a machine learning algorithm is used to predict the unknown temperature by taking full advantage of multiple resonances. The results show the average error of 3.8 × 10-3°C within the range from 25.00°C to 40.00°C by employing a generalized regression neural network (GRNN). In addition, we have also discussed the influence of the consumed data resource on its predicted performance, such as the amount of training data and the case of different temperate ranges between the training and test data. With high accuracy and large dynamic range, this work paves the way for WGM resonator-based intelligent optical sensing.

20.
Hepatol Int ; 17(5): 1192-1204, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37258989

RESUMO

BACKGROUND AND AIM: Baveno VII workshop recommends management of acute variceal bleeding (AVB) in cirrhotic patients with nonmalignant portal vein thrombosis (PVT) should be performed according to the guidelines for patients without PVT. Nevertheless, whether PVT affects the outcome of patients with cirrhosis and AVB remains unclear. The aim of this study was to assess the clinical impact of PVT on the outcomes in the pre-emptive TIPSS eligible patients with cirrhosis and AVB. METHODS: From December 2010 to June 2016, 1219 consecutive cirrhotic patients admitted due to AVB with (n = 151; 12.4%) or without PVT (n = 1068; 87.6%), who received drug plus endoscopic treatment (a combination of vasoactive drugs, antibiotics, and endoscopic ligation for AVB, followed by beta-blockers plus variceal ligation for prevention of rebleeding) were retrospectively included. Fine and Gray competing risk regression models were taken to evaluate the impact of PVT on clinical outcomes after adjusting for potential confounders. RESULTS: During follow-up, 211 patients (17.3%) died, 490 (40.2%) experienced further bleeding, and 78 (6.4%) experienced new or worsening ascites within 1 year. Compared with those without PVT, patients with PVT had a similar risk of mortality (PVT vs no-PVT: 19.9% vs 16.7% at 1 year; adjusted HR 0.88, 95%CI 0.51-1.52, p = 0.653), further bleeding (47.0% vs 39.2% at 1 year, adjusted HR 1.19, 95% CI 0.92-1.53, p = 183), and new or worsening ascites (7.9% vs 9.6%, adjusted HR 0.70, 95% CI 0.39-1.28, p = 0.253) after adjusting for confounders in multivariable models. These findings were consistent across different relevant subgroups and confirmed by propensity score matching analysis. CONCLUSIONS: Our study showed no evidence that the PVT was associated with an improved or worsened outcome among cirrhotic patients with AVB who received standard treatment.


Assuntos
Varizes Esofágicas e Gástricas , Derivação Portossistêmica Transjugular Intra-Hepática , Trombose Venosa , Humanos , Varizes Esofágicas e Gástricas/etiologia , Veia Porta/patologia , Estudos Retrospectivos , Ascite/complicações , Hemorragia Gastrointestinal/prevenção & controle , Cirrose Hepática/patologia , Fibrose , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Trombose Venosa/etiologia , Resultado do Tratamento
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