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1.
J Org Chem ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38845522

RESUMO

A one-pot approach has been developed for the synthesis of α-ketothioamide derivatives from sulfur ylides, nitrosobenzenes, and thioacetic acid. This protocol is carried out under mild reaction conditions in generally moderate to excellent yields without any precious catalysts, affording the derivatives with structural diversity. Additionally, a possible mechanism for this chemical transformation is proposed.

2.
ISA Trans ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38851926

RESUMO

When legged robots perform complex tasks in unstructured environments, falls are inevitable due to unknown external disturbances. However, current research mainly focuses on the locomotion control of legged robots without falling. This paper proposes a comprehensive decision-making and control framework to address the falling over of quadruped robots. First, a capturability-based fall prediction algorithm is derived for planar single-contact and 3D multi-contact locomotion with a predefined gait sequence. For safe fall control, a novel contact-implicit trajectory optimization method is proposed to generate both state and input trajectories and contact mode sequences. Specifically, incorporating uncertainty into the system and terrain models enables mitigating the non-smoothness of contact dynamics while improving the robustness of the resulting trajectories. Furthermore, a model-free deep reinforcement learning-based approach is presented to achieve fall recovery after the robot completes a fall. Experimental results demonstrate that the proposed fall prediction algorithm accurately predicts robot falls with up to 95% accuracy approximately 395ms in advance. Compared to classical locomotion controllers, which often struggle to maintain balance under significant pushes or terrain perturbations, the presented framework can autonomously switch to the fall controller approximately 0.06s after the perturbation, effectively preventing falls or achieving recovery with a threefold reduction in touchdown impact velocity. These findings highlight the effectiveness of the proposed framework in enhancing the stability and safety of legged robots in unstructured environments.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38829448

RESUMO

The relationship between infectious agents and autoimmune diseases is a complex issue. In recent years, increasing clinical cases have indicated that infectious agents play an important role in the development of autoimmune diseases. Molecular mimicry is currently widely regarded as the primary pathogenic mechanism of various autoimmune diseases in humans. Components of infectious agents can undergo molecular mimicry with components in patients' bodies, leading to the development of various autoimmune diseases. In this article, we provide a brief overview of current research of the current research status on the relationship between infectious agents and autoimmune diseases, and describe our current understanding of their mechanisms of action in order to better understand the pathogenesis, diagnosis, and treatment of autoimmune diseases.

4.
Am J Cancer Res ; 14(5): 2037-2054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859843

RESUMO

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

5.
Food Res Int ; 189: 114533, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876603

RESUMO

Glutinous rice is extensively consumed due to its nutritious content and wonderful flavor. However, glutinous rice flour has a high glycemic index, and the storage deterioration of sweet dumplingsissevere. Transglutaminase (TG) was used to cross-link glutinous rice protein and improve the characteristics of glutinous rice products. The findings demonstrated that TG significantly catalysed protein cross-linking to form a dense protein network, reduced the viscosity of glutinous rice paste and improved the thermal stability. The protein network may physically block the access of starch granules to digestive enzymes to lower the digestion rate of starch, and attenuate the damage of ice crystal molecules to the starch structure to improve the freezing stability of starch gels. The cracking rate and water loss of sweet dumplings prepared using glutinous rice flour with TG treated for 60 min reduced significantly. In conclusion, this study broadened the application of TG in starch products.


Assuntos
Digestão , Farinha , Manipulação de Alimentos , Oryza , Amido , Transglutaminases , Oryza/química , Transglutaminases/metabolismo , Amido/metabolismo , Amido/química , Farinha/análise , Manipulação de Alimentos/métodos , Viscosidade , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química
6.
Nanomaterials (Basel) ; 14(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38869610

RESUMO

Crosslinked polyethylene (XLPE) is an important polyethylene modification material which is widely used in high-voltage direct current (HVDC) transmission systems. Low-density polyethylene (LDPE) was used as a matrix to improve the thermal and electrical properties of XLPE composites through the synergistic effect of a crosslinking agent and nanopore structure molecular sieve, TS-1. It was found that the electrical and thermal properties of the matrices were different due to the crosslinking degree and crosslinking efficiency, and the introduction of TS-1 enhanced the dielectric constants of the two matrices to 2.53 and 2.54, and the direct current (DC) resistivities were increased to 3 × 1012 and 4 × 1012 Ω·m, with the enhancement of the thermal conductivity at different temperatures. As the applied voltage increases, the DC breakdown field strength is enhanced from 318 to 363 kV/mm and 330 to 356 kV/mm. The unique nanopore structure of TS-1 itself can inhibit the injection and accumulation in the internal space of crosslinked polyethylene composites, and the pore size effect of the filler can limit the development of electron impact ionization, inhibit the electron avalanche breakdown, and improve the strength of the external applied electric field (breakdown field) that TS-1/XLPE nanocomposites can withstand. This provides a new method for the preparation of nanocomposite insulating dielectric materials for HVDC transmission systems with better performance.

7.
Adv Mater ; : e2404811, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875445

RESUMO

Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion, slow adhesion formation, cytotoxicity concerns, and lack of antibacterial properties. Herein, an injectable hydrogel (denoted as ES gel) with rapid, robust adhesive sealing and inherent antibacterial activity based on ε-polylysine and a poly(ethylene glycol) derivative is developed. The engineered hydrogel exhibits rapid gelation behavior, high mechanical strength, strong adhesion to various tissues, and can sustain an ultrahigh burst pressure of 450 mmHg. It also presents excellent biocompatibility, biodegradability, antibacterial properties, and on-demand removability. Significantly improved hemostatic efficacy of ES gel compared to fibrin glue is demonstrated using various injury models in rats and rabbits. Remarkably, the adhesive hydrogel can effectively halt lethal non-compressible hemorrhages in visceral organs (liver, spleen, and heart) and femoral artery injury models in fully anticoagulated pigs. Furthermore, the hydrogel outperforms commercial products in sutureless wound closure and repair in the rat liver defect, skin incision, and infected full-thickness skin wound models. Overall, this study highlights the promising clinical applications of ES gel for managing uncontrolled hemorrhage, sutureless wound closure, and infected wound repair. This article is protected by copyright. All rights reserved.

8.
Aesthetic Plast Surg ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839614

RESUMO

BACKGROUND: Deviation and asymmetry relapse after secondary unilateral cleft rhinoplasty with septal extension graft is a common yet serious problem especially among Asian patients. Therefore, finding an effective approach to reduce deformity relapse remains a great challenge to plastic surgeons. METHODS: In this study, authors established finite element models to simulate different nasal cartilage-corrected options and different reinforcing strategies in secondary unilateral cleft rhinoplasty. A load of 0.01N was given to the nasal tip to simulate the soft tissue pressure, while two loads of 0.5N were separately given to the anterior and posterior part of the septal extension graft to simulate the rhinoplasty condition. Maximum deformations were evaluated to make stability judgments. RESULTS: The maximum deformation of different cartilage correction models in ascending order was: UCL deformity with septum correction, normal nasal cartilage, UCL nasal deformity, and UCL nasal deformity with lower lateral cartilage correction. When applied L-strut reinforcement graft was harvested from the perpendicular plate of the ethmoid bone, the maximum deformation of the models decreased significantly, and strong fixation of the septum could further enhance this decreasing effect. CONCLUSIONS: Correcting the septum and lower lateral cartilage together could improve the structural stability and symmetry in secondary unilateral cleft rhinoplasty. To keep the corrected septum stable and thus reduce deformity relapse, reinforcing the L-strut with perpendicular plate of ethmoid graft while strongly anchoring the septal cartilage to the anterior nasal spine was proved to be effective in both finite element analysis and clinical observation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

9.
Theor Appl Genet ; 137(7): 158, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864891

RESUMO

Examining the connection between P and starch-related signals can help elucidate the balance between nutrients and yield. This study utilized 307 diverse maize inbred lines to conduct multi-year and multi-plot trials, aiming to explore the relationship among P content, starch content, and 100-kernel weight (HKW) of mature grains. A significant negative correlation was found between P content and both starch content and HKW, while starch content showed a positive correlation with HKW. The starch granules in grains with high-P and low-starch content (HPLS) were significantly smaller compared to grains with low-P high-starch content (LPHS). Additionally, mian04185-4 (HPLS) exhibited irregular and loosely packed starch granules. A significant decrease in ZmPHOs genes expression was detected in the HPLS line ZNC442 as compared to the LPHS line SCML0849, while no expression difference was observed in AGPase encoding genes between these two lines. The down-regulated genes in ZNC442 grains were enriched in nucleotide sugar and fatty acid anabolic pathways, while up-regulated genes were enriched in the ABC transporters pathway. An accelerated breakdown of fat as the P content increased was also observed. This implied that HPLS was resulted from elevated lipid decomposition and inadequate carbon sources. The GWAS analysis identified 514 significantly associated genes, out of which 248 were differentially expressed. Zm00001d052392 was found to be significantly associated with P content/HKW, exhibiting high expression in SCML0849 but almost no expression in ZNC442. Overall, these findings suggested new approaches for achieving a P-yield balance through the manipulation of lipid metabolic pathways in grains.


Assuntos
Fósforo , Amido , Transcriptoma , Zea mays , Zea mays/genética , Zea mays/metabolismo , Amido/metabolismo , Fósforo/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Fenótipo
10.
ACS Synth Biol ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825826

RESUMO

Gas-fermenting Clostridium species hold tremendous promise for one-carbon biomanufacturing. To unlock their full potential, it is crucial to unravel and optimize the intricate regulatory networks that govern these organisms; however, this aspect is currently underexplored. In this study, we employed pooled CRISPR interference (CRISPRi) screening to uncover a wide range of functional transcription factors (TFs) in Clostridium ljungdahlii, a representative species of gas-fermenting Clostridium, with a special focus on TFs associated with the utilization of carbon resources. Among the 425 TF candidates, we identified 75 and 68 TF genes affecting the heterotrophic and autotrophic growth of C. ljungdahlii, respectively. We focused our attention on two of the screened TFs, NrdR and DeoR, and revealed their pivotal roles in the regulation of deoxyribonucleoside triphosphates (dNTPs) supply, carbon fixation, and product synthesis in C. ljungdahlii, thereby influencing the strain performance in gas fermentation. Based on this, we proceeded to optimize the expression of deoR in C. ljungdahlii by adjusting its promoter strength, leading to an improved growth rate and ethanol synthesis of C. ljungdahlii when utilizing syngas. This study highlights the effectiveness of pooled CRISPRi screening in gas-fermenting Clostridium species, expanding the horizons for functional genomic research in these industrially important bacteria.

11.
Ying Yong Sheng Tai Xue Bao ; 35(4): 961-969, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38884231

RESUMO

Research about feeding ecology of fish is important to understand individual behavior and population development, which is also the basic to analyze trophic structure and function of aquatic ecosystems. Chaetrichthys stigmatias is one of the key species in the Haizhou Bay fisheries ecosystem, which has critical ecological niche within the food web. In this study, we collected samples through bottom trawl surveys during the fall of 2018 in the Haizhou Bay, and analyzed the feeding ecology of C. stigmatias based on both stomach content analysis and stable isotope technology. The results showed that the primary diet groups for C. stigmatias were Ophiuroidea and Shrimp, including Ophiothrix marenzelleri, Ophiopholis mirabilis, Ophiura sarsii, Penaeidae, and Alpheus japonicus. The range of δ13C values of C. stigmatias was from -19.39‰ to -15.74‰, with an average value of (-18.07±0.87)‰, which had no significant correlation with body length. The range of δ15N values was from 8.16‰ to 12.86‰, with an average value of (10.14±1.51)‰, which was positively correlated with body length. The trophic level of C. stigmatias showed a positive relationship with body length, with an average value of (3.74±0.34) and a range value of 3.32 to 4.20 among different size groups. The contribution rates of different prey groups varied significantly. Based on the structural equation modeling, we found that the feeding intensity of C. stigmatias was primally influenced by body length, sea bottom salinity, sea bottom temperature, and water depth, with a particularly signi-ficant positive correlation with body length. The combination of stable isotope technology and stomach content analysis methods could contribute to comprehensive understanding on the feeding ecology of C. stigmatias, providing essential data and foundation for research on trophic structures and resource conservation in the Haizhou Bay ecosystem.


Assuntos
Baías , Ecossistema , Comportamento Alimentar , Estações do Ano , Animais , China , Cadeia Alimentar , Peixes , Oceanos e Mares , Conteúdo Gastrointestinal/química
12.
Zhen Ci Yan Jiu ; 49(5): 526-533, 2024 May 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38764125

RESUMO

Lumbar intervertebral disc herniation (LDH) is a common and frequently-occurring disease, which usually causes lumbar and leg pain. Studies have shown that acupuncture can improve the symptoms of LDH patients. In the present paper, we summarize the progress of researches on the mechanisms of acupuncture underlying improvement of symptoms of LDH in recent 10 years from 1) delaying the intervertibral disc degeneration (by down-regulating the expressions of matrix metalloproteinase ï¼»MMPï¼½-3 and MMP-4, up-regulating the expressions of diosaccharides and polyglycoprotein, inhibiting apoptosis and promoting mitochondrial autophagy of nucleus pulposus cells, etc.), 2) maintaining spinal column stability (by relieving rachiasmus and improving lumbar flexor and extensor muscle strength, lowering the degree of polyfidus edema and fat infiltration, and restoring the biomechanics of the spine), 3) regulating inflammation (by inhibiting the production of proinflammatory factors and increasing the production of anti-inflammatory factors, etc.), 4) regulating immune response (by promoting the activity of T cells and other immune cells, lowering serum levels of MMP-3, transforming growth factor-ß1 and prostaglandin E2, raising serum levels of IgA, IgG and IgM to improve immune function ), 5) modulating neural structure and function (by promoting myelin regeneration of sciatic nerve fibers, and reducing the edema of Schwann cells' cytoplasm and mitochondria, and improving neural ultrastructure, and sensory and motor functions of peripheral nerves, etc.), 6) relieving lumbar pain (by down-regulating expression of Ca2+/calmodulin-dependent protein kinase and activation of lumbar spinal cord glial cells, blocking nociceptive signal conduction, regulating the levels of pain-related factors, etc.), and 7) improving local microcirculation. These results may provide scientific evidence for acupuncture treatment of LDH.


Assuntos
Terapia por Acupuntura , Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/terapia , Animais , Vértebras Lombares
13.
J Patient Rep Outcomes ; 8(1): 53, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816587

RESUMO

BACKGROUND: There is no gold standard patient-reported outcome measure (PROM) in hand surgery. As a result, a diverse array of PROM instruments have been utilized across centers over time. Lack of score interchangeability limits the ability to compare or conglomerate scores when new instruments are introduced. Our aim was to develop a linkage for the PROMIS UE CAT v1.2 and PROMIS PF CAT scores and develop crosswalk tables for interconversion between these PROMs. METHODS: Retrospective review was conducted to identify adult (≥ 18y) patients seen by orthopaedic hand surgeons at a single academic tertiary care hospital who had completed PROMIS UE CAT v1.2 and PROMIS PF CAT score at the same visit. For those with multiple visits, only one randomly selected visit was included in the analyses. Pearson's correlation was calculated to determine the linear relationship between the scores. Linkage from PF to UE was performed utilizing several commonly utilized equating models (identity, mean, linear, equipercentile and circle-arc methods). The performance of the models was assessed using intraclass correlation (ICC) between observed PROMIS UE CAT v1.2 and estimated PROMIS UE CAT v1.2 scores generated using the model as well as Root Mean Square Error (RMSE). The model chosen as the 'best' was further assessed for population invariance using root expected mean squared difference (REMSD) where < 0.08 were considered good. RESULTS: Of 10,081 included patients, mean age was 48.3 (SD = 17.0), and 54% were female (5,477/10,081). Mean UE CAT v1.2 and PF CAT scores were 37 (SD = 9.8) and 46 (SD = 10.0), respectively. There was a strong correlation between the scores (Pearson correlation r = 0.70). All methods performed acceptably (ICC ≥ 0.66 and RMSE < = 7.52 for all). The equipercentile method had the highest ICC (ICC = 0.70 (95% CI 0.69-0.71)) while the mean and circle arc methods had the lowest RMSE. The circle arc method is the most reliable with the smallest standard error and has satisfactory population invariance across age group (REMSD 0.065) and sex (REMSD 0.036). CONCLUSIONS: Crosswalk tables to be used for bidirectional conversion between scores were created. LEVEL OF EVIDENCE: III.


Assuntos
Mãos , Medidas de Resultados Relatados pelo Paciente , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Mãos/cirurgia , Adulto , Extremidade Superior/cirurgia , Idoso
14.
Orthop Surg ; 16(6): 1434-1444, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38693602

RESUMO

OBJECTIVE: The volume based procurement (VBP) program in China was initiated in 2022. The cost-effectiveness of robotic arm assisted total knee arthroplasty is yet uncertain after the initiation of the program. The objective of the study was to investigate the cost-effectiveness of robotic arm-assisted total knee arthroplasty and the influence of the VBP program to its cost-effectiveness in China. METHODS: The study was a Markov model-based cost-effectiveness study. Cases of primary total knee arthroplasty from January 2019 to December 2021 were included retrospectively. A Markov model was developed to simulate patients with advanced knee osteoarthritis. Manual and robotic arm-assisted total knee arthroplasties were compared for cost-effectiveness before and after the engagement of the VBP program in China. Probability and sensitivity analysis were conducted. RESULTS: Robotic arm-assisted total knee arthroplasty showed better recovery and lower revision rates before and after initiation of the VBP program. Robotic arm-based TKA was superior to manual total knee arthroplasty, with an increased effectiveness of 0.26 (16.87 vs 16.61) before and 0.52 (16.96 vs 16.43) after the application of Volume-based procurement, respectively. The procedure is more cost-effective in the new procurement system (17.13 vs 16.89). Costs of manual or robotic arm-assisted TKA were the most sensitive parameters in our model. CONCLUSION: Based on previous and current medical charging systems in China, robotic arm-assisted total knee arthroplasty is a more cost-effective procedure compared to traditional manual total knee arthroplasty. As the volume-based procurement VBP program shows, the procedure can be more cost-effective.


Assuntos
Artroplastia do Joelho , Análise Custo-Benefício , Cadeias de Markov , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/economia , Artroplastia do Joelho/métodos , China , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/economia
15.
Sci Total Environ ; 938: 173514, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38802015

RESUMO

Groundwater depletion in intensively exploited aquifers of China has been widely recognized, whereas an overall examination of groundwater storage (GWS) changes over major aquifers remains challenging due to limited data and notable uncertainties. Here, we present a study to explore GWS changes over eighteen major aquifers covering an area of 1,680,000 km2 in China using data obtained from the Gravity Recovery and Climate Experiments (GRACE), global models, and in-situ groundwater level observations. The analysis aims to reveal the discrepancy in annual trends, amplitudes, and phases associated with GWS changes among different aquifers. It is found that GWS changes in the studied aquifers represent a spatial pattern of 'Wet-gets-more, Dry-gets-less'. An overall decreasing trend of -4.65 ± 0.34 km3/yr is observed by GRACE from 2005 to 2016, consisting of a significant (p < 0.05) increase of 47.28 ± 3.48 km3 in 7 aquifers and decrease of 103.56 ± 2.4 km3 (∼2.6 times the full storage capacity of the Three Gorges Reservoir) in 10 aquifers summed over the 12 years. The annual GWS normally reaches a peak in late July with an area-weighted average annual amplitude of 19 mm, showing notable discrepancy in phases and amplitudes between the losing aquifers (12 mm in middle August) in northern China and gaining aquifers (28 mm in early July) mostly in southern China. GRACE estimates are generally comparable, but can be notably different, with the results obtained from model simulations and in-situ observations at aquifer scale, with the area-weighted average correlation coefficients of 0.6 and 0.5, respectively. This study highlights different GWS changes of losing and gaining aquifers in response to coupled impacts of hydrogeology, climate and human interventions, and calls for divergent adaptions in regional groundwater management.

16.
Adv Mater ; : e2400683, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747891

RESUMO

As electric vehicles, portable electronic devices, and tools have increasingly high requirements for battery energy density and power density, constantly improving battery performance is a research focus. Accurate measurement of the structure-activity relationship of active materials is key to advancing the research of high-performance batteries. However, conventional performance tests of active materials are based on the electrochemical measurement of porous composite electrodes containing active materials, polymer binders, and conductive carbon additives, which cannot establish an accurate structure-activity relationship with the physical characterization of microregions. In this review, in order to promote the accurate measurement and understanding of the structure-activity relationship of materials, the electrochemical measurement and physical characterization of energy storage materials at single-particle scale are reviewed. The potential problems and possible improvement schemes of the single particle electrochemical measurement and physical characterization are proposed. Their potential applications in single particle electrochemical simulation and machine learning are prospected. This review aims to promote the further application of single particle electrochemical measurement and physical characterization in energy storage materials, hoping to achieve 3D unified evaluation of physical characterization, electrochemical measurement, and theoretical simulation at the single particle scale to provide new inspiration for the development of high-performance batteries.

17.
Int J Biol Sci ; 20(7): 2440-2453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725860

RESUMO

Glioblastoma is the prevailing and highly malignant form of primary brain neoplasm with poor prognosis. Exosomes derived from glioblastoma cells act a vital role in malignant progression via regulating tumor microenvironment (TME), exosomal tetraspanin protein family members (TSPANs) are important actors of cell communication in TME. Among all the TSPANs, TSPAN6 exhibited predominantly higher expression levels in comparison to normal tissues. Meanwhile, glioblastoma patients with high level of TSPAN6 had shorter overall survival compared with low level of TSPAN6. Furthermore, TSPAN6 promoted the malignant progression of glioblastoma via promoting the proliferation and metastatic potential of glioblastoma cells. More interestingly, TSPAN6 overexpression in glioblastoma cells promoted the migration of vascular endothelial cell, and exosome secretion inhibitor reversed the migrative ability of vascular endothelial cells enhanced by TSPAN6 overexpressing glioblastoma cells, indicating that TSPAN6 might reinforce angiogenesis via exosomes in TME. Mechanistically, TSPAN6 enhanced the malignant progression of glioblastoma by interacting with CDK5RAP3 and regulating STAT3 signaling pathway. In addition, TSPAN6 overexpression in glioblastoma cells enhanced angiogenesis via regulating TME and STAT3 signaling pathway. Collectively, TSPAN6 has the potential to serve as both a therapeutic target and a prognostic biomarker for the treatment of glioblastoma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Fator de Transcrição STAT3 , Transdução de Sinais , Tetraspaninas , Animais , Humanos , Camundongos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Exossomos/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fator de Transcrição STAT3/metabolismo , Tetraspaninas/metabolismo , Tetraspaninas/genética
18.
Cancer Cell ; 42(6): 1067-1085.e11, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38759655

RESUMO

In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM.


Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Transição Epitelial-Mesenquimal , Melanoma , Invasividade Neoplásica , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Transição Epitelial-Mesenquimal/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos CD/metabolismo , Antígenos CD/genética , Apolipoproteínas E/genética , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Feminino , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Análise Espacial , Pessoa de Meia-Idade , Prognóstico , Progressão da Doença , Idoso , Receptores de Superfície Celular
19.
Artigo em Inglês | MEDLINE | ID: mdl-38754540

RESUMO

BACKGROUND: The purpose of this study is to evaluate the relationship between multiple radiographic measures of lateralization and distalization and clinical outcome scores after reverse total shoulder arthroplasty (RTSA). METHODS: We retrospectively evaluated all RTSAs performed by the senior author between January 1, 2007, and November 1, 2017. We then evaluated the visual analog scale for pain (VAS pain), Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) scores and complication and reoperation rates at a minimum of 2-year follow-up. We measured preoperative and postoperative (2-week) radiographs for the lateralization shoulder angle (LSA), the distalization shoulder angle (DSA), lateral humeral offset (LHO), and distance from glenoid to lateral aspect of the greater tuberosity (GLAGT). A multivariable analysis was performed evaluating the effect of the postoperative radiographic measurements on final patient reported outcomes (ASES scores, SST, VAS pain). RESULTS: The cohort included 216 shoulders from unique patients who had patient reported outcome scores available at a minimum of 2-year follow-up (average, 4.0±1.9 years) for a total follow-up rate of 70%. In the multivariable models, more lateralization (LSA) was associated with worse final ASES scores -0.52 (95% CI: -0.88 to -0.17; p=0.004), and more distalization (DSA) was associated with better final ASES scores 0.40 (95% CI: 0.11, 0.69; p=0.007). More lateralization (LSA) was associated with worse final SST scores -0.06 (95% CI: -0.11, -0.003; p=0.039). Finally, greater distalization (DSA) was associated with lower final VAS pain scores, Ratio = 0.98 (95% CI: 0.96, 1.00; p=0.021). CONCLUSION: Greater distalization and less lateralization are associated with better function and less pain after Grammont-style RTSA. If utilizing a Grammont-style implant, remaining consistent with Grammont's principles of implant placement will afford better final clinical outcomes.

20.
Aesthetic Plast Surg ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789808

RESUMO

BACKGROUND: Secondary unilateral cleft lip deformities are commonly observed in patients with cleft lip and traditional surgical methods can't completely tackle this problem. The purpose of this study was to evaluate the outcomes of a novel surgical technique using force balance reconstruction of the orbicularis oris. METHODS: 53 patients with secondary unilateral cleft lip deformity were included in this study, in which the orbicularis oris muscle was reconstructed symmetrically to achieve optimal force balance. Photometric 2d indexes were employed to evaluate the outcome of 27 patients, and 3d indexes for the remaining 26 patients. Aesthetic evaluation and parent-patient satisfaction surveys were also recorded. RESULTS: Significant differences were found in the following: (1) LH (the lip height), LW (the lip width), D1(the vertical distance from the white roll to the vermilion bottom at the christa philtra points) and D2(the vertical distance from the christa philtra points to the facial midline) when comparing preoperative and postoperative 2D images; (2) LH, LW, D1 and D2 when comparing preoperative and follow-up 2D images; (3) RMS (root mean of square) when comparing preoperative and postoperative 3D images. Aesthetic evaluation in the follow-up period was a mean of 4.29, while parent-patient satisfaction of the overall appearance was a mean of 4.41. CONCLUSIONS: The results suggest this new muscle reconstruction technique can significantly improve the surgical outcome of secondary unilateral cleft lip deformities. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ."

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