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Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.
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Macrófagos , Monocitos , Trombosis de la Vena , Humanos , Monocitos/inmunología , Monocitos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Trombosis de la Vena/inmunología , Trombosis de la Vena/metabolismo , Tromboembolia Venosa/inmunología , Tromboembolia Venosa/patología , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
A surge of public interest in NMN supplementation has been observed in recent years. However, whether NMN supplements are effective in improving metabolic health remains unclear. The objective of the review was to assess the effects of NMN supplementation on fasting glucose, triglycerides, total cholesterol, LDL-C, and HDL-C in adults. Studies were located by searching four databases (PubMed, Embase, Cochrane, and Web of Science). Two reviewers independently conducted title/abstract and full-text screening, data extraction, and risk-of-bias assessment. Of the 4049 records reviewed, 12 studies with a total of 513 participants met the criteria for analysis. Random-effects meta-analyses found an overall significant effect of NMN supplementation in elevating blood NAD levels. However, most of the clinically relevant outcomes were not significantly different between NMN supplementation and control group. Risk-of-bias assessment using RoB2 showed some concerns in seven studies and high risk of bias in the other five studies. Together, our findings suggest that an exaggeration of the benefits of NMN supplementation may exist in the field. Although the limited number of eligible studies was sufficiently powered to detect changes in the abovementioned primary outcomes, more studies are needed to conclude about the exact effects of NMN supplementation.
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Lambda-cyhalothrin (LCT) is a common pyrethroid insecticide widely used for ectoparasite control and hygiene pest prevention in poultry and this study aimed to investigate the mechanisms of LCT-induced cardiac injury in chickens. Low, medium, and high-dose LCT exposure models in chickens were established and hematoxylin and eosin (H&E) staining, dihydroethidium (DHE) staining, TUNEL staining, immunofluorescence, biochemical analysis, and gene expression analysis were used to study the effects of LCT exposure on the chicken heart. The results showed that LCT exposure increased the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), led to muscle fiber breakage and inflammatory cell infiltration and caused cardiac tissue damage. The DHE staining and biochemical analysis revealed that LCT exposure resulted in the excessive accumulation of ROS, decreased activities/levels of catalase (CAT), total superoxide dismutase (T-SOD), and glutathione (GSH), and increased levels of the oxidative damage marker malondialdehyde (MDA). The TUNEL staining indicated that LCT exposure increased apoptosis possibly through the elevated expression of pro-apoptotic genes in the mitochondrial pathway, the reduced expression of anti-apoptotic genes, the upregulation of pro-inflammatory factors and the downregulation of anti-inflammatory factors. Here, LCT exposure significantly inhibited the expression of genes in the Nrf2/HO-1 pathway and activated the expression of genes in the CYP450 enzyme system. Compared to the low-dose group, the high-dose LCT exposure group showed lower levels of apoptosis and inflammation, possibly related to the low oxidative stress levels mediated by the decreased expression of the CYP450 enzyme system. In conclusion, LCT exposure induces oxidative stress, apoptosis, and inflammation in chicken hearts, which may be associated with the inhibition of the Nrf2/HO-1 pathway and activation of the CYP450 enzyme system. This study provides a theoretical basis for the safer use of insecticides in poultry production.
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Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages. Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration, which is a prerequisite for nerve regeneration, we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis. Herein, we found low expression of microRNA-301a in intact sciatic nerves, with no impact of the microRNA-301a knockout on nerve structure and function. By contrast, we found significant upregulation of microRNA- 301a in injured sciatic nerves. We established a sciatic nerve crush model in microRNA-301a knockout mice, which exhibited attenuated morphological and functional regeneration following sciatic nerve crush injury. The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model. Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration, which was reversible under transfection with microRNA-301a mimics. Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a. Combined with our previous findings in macrophages, we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.
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INTRODUCTION: Bedsharing is common but advised against by the American Academy of Pediatrics. It is unknown if breastfeeding physicians bedshare more or less than the general population. OBJECTIVES: To determine the prevalence of bedsharing among physicians, their reasons for bedsharing or not, and whether bedsharing was associated with a longer duration of breastfeeding. METHODS: An online survey was adapted from surveys administered by the Centers for Disease Control and Prevention. The survey was administered to physicians and medical students who birthed children from October 2020 through August 2021. Respondents were asked to report on a singleton birth, and questions centered around sleep practices and breastfeeding. Survival analysis was used to examine the association between bedsharing and breastfeeding duration. RESULTS: Of 546 respondents with bedsharing data, 68% reported some history of bedsharing, and 77% were in specialties that involved caring for pregnant people and/or infants. Those who bedshared breastfed an average of four months longer than those who never bedshared (18.08 versus 14.08 months p<0.001). The adjusted risk of breastfeeding cessation was markedly lower for those who bedshared compared to those who did not (Hazard Ratio 0.57, 95% Confidence Interval 0.45, 0.71). The primary reason for bedsharing was to breastfeed (73%); the primary reason for not bedsharing was safety concerns (92%). Among those who bedshared (n = 373), 52% did not inform their child's healthcare provider. CONCLUSIONS: Bedsharing is common among our sample of mainly breastfeeding physicians, including those who care for pregnant people and/or infants. It is also associated with a longer duration of breastfeeding, which has implications for population health. Practicing bedsharing implies cognitive dissidence and may affect how physicians counsel about bedsharing. Additionally, lack of disclosure of bedsharing practices has implications for practical guidance about having open non-judgmental conversations and may be a missed opportunity to counsel on bedsharing safety.
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Lactancia Materna , Médicos , Sueño , Humanos , Lactancia Materna/estadística & datos numéricos , Femenino , Médicos/estadística & datos numéricos , Médicos/psicología , Encuestas y Cuestionarios , Masculino , Adulto , Persona de Mediana Edad , Lactante , Recién Nacido , Lechos , EmbarazoRESUMEN
Motion retargeting is an active research area in computer graphics and animation, allowing for the transfer of motion from one character to another, thereby creating diverse animated character data. While this technology has numerous applications in animation, games, and movies, current methods often produce unnatural or semantically inconsistent motion when applied to characters with different shapes or joint counts. This is primarily due to a lack of consideration for the geometric and spatial relationships between the body parts of the source and target characters. To tackle this challenge, we introduce a novel spatially-preserving Skinned Motion Retargeting Network (SMRNet) capable of handling motion retargeting for characters with varying shapes and skeletal structures while maintaining semantic consistency. By learning a hybrid representation of the character's skeleton and shape in a rest pose, SMRNet transfers the rotation and root joint position of the source character's motion to the target character through embedded rest pose feature alignment. Additionally, it incorporates a differentiable loss function to further preserve the spatial consistency of body parts between the source and target. Comprehensive quantitative and qualitative evaluations demonstrate the superiority of our approach over existing alternatives, particularly in preserving spatial relationships more effectively.
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BACKGROUND: The efficacy of lymph node dissection (LND) and oncological outcomes of robot-assisted (RL) versus video-assisted thoracoscopic lobectomy (VL) for non-small cell lung cancer (NSCLC) with nodal involvement remains controversial. This study aims to compare LND quality and early recurrence (ER) rate between RL and VL for stage N1-2 NSCLC patients based on eleven-year real-world data from a high-volume center. METHODS: Pathologic stage IIB-IIIB (T1-3N1-2) NSCLC patients undergoing RL or VL in Shanghai Chest Hospital from 2010 to 2021 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM, 1:4 RL versus VL) was performed to mitigate baseline differences. LND quality was evaluated by adequate (≥16) LND and nodal upstaging rates. ER was defined as recurrence occurring within 24 months post-surgery. RESULTS: Out of 1578 cases reviewed, PSM yielded 200 RL and 800 VL cases. Without compromising perioperative outcomes, RL assessed more N1 and N2 LNs and N1 stations, and led to higher incidences of adequate LND (58.5 % vs. 42.0 %, p < 0.001) and nodal upstaging (p = 0.026), compared to VL. Notably, RL improved perioperative outcomes for patients undergoing adequate LND than VL. Finally, RL notably reduced ER rate (22.0 % vs. 29.6 %, p = 0.032), especially LN ER rate (15.0 % vs. 21.5 %, p = 0.041), and prolonged disease-free survival (DFS; hazard ratio = 0.837, p = 0.040) compared with VL. Further subgroup analysis of ER and DFS within the cN1-2-stage cohort verified this survival benefit. CONCLUSIONS: RL surpasses VL in enhancing LND quality, reducing ER rates, and improving perioperative outcomes when adequate LND is performed for stage N1-2 NSCLC patients.
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BACKGROUND & AIMS: The association between artificial sweeteners and various cancers has been investigated, but their relationship with respiratory system cancers remains uncertain. To address this knowledge gap, we conducted a comprehensive Mendelian Randomization (MR) analysis. METHODS: We looked for SNPs associated with artificial sweetener intake and respiratory system cancers from the IEU OpenGWAS project, as well as SNPs related to sweet taste in artificial sweeteners from Hwang et al.'s study. Rigorous quality control procedures were implemented to select instrumental Single Nucleotide Polymorphisms that were closely linked to artificial sweetener intake. To ensure the reliability of our findings, we employed five different analytical methods, with the inverse variance weighting method being the primary approach. Additionally, we thoroughly assessed heterogeneity, pleiotropy, and sensitivity. Finally, we conducted Multivariable Mendelian Randomization (MVMR) to validate our results. RESULTS: Intake of artificial sweetener added to cereal showed a positive association with malignant neoplasm of the lip, oral cavity, and pharynx (OR: 1027.54; 95% CI: 4.8-219994.46; P = 0.011), and the result was also confirmed by the MVMR analysis. In addition, better perceived intensity of aspartame was negatively associated with cancers in these regions (OR: 0.49; 95% CI: 0.28-0.88; P = 0.016). Intake of artificial sweetener added to coffee or tea was not related with respiratory system cancer. CONCLUSIONS: Our research offers evidence that the consumption of artificial sweeteners in cereals could increase the risk of cancers in the lip, oral cavity, and pharynx. Additionally, a greater sensitivity to the taste of aspartame may lower this risk.
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Targeted regulation using transgrafting technology has become a trend. However, the mechanisms of transgene-derived signal communication between rootstocks and scions remain unclear in woody plants. Here, we grafted wild-type (WT) walnut (Juglans regia L.) on WT (WT/WT), JrGA20ox1 (encodes a gibberellin 20-oxidase)-overexpressing (WT/OE), and JrGA20ox1-RNAi transformation (WT/RNAi) walnut in vitro. We aimed to elucidate the mechanisms of JrGA20ox1-derived signal communication under PEG-simulated drought stress between rootstocks and scions in walnut. We demonstrated that JrGA20ox1-OE and JrGA20ox1-RNAi rootstocks could transport active gibberellins (GAs) and JrGA20ox1-RNAi vector-produced sRNAs to WT scions under PEG-simulated drought stress, respectively. The movement of sRNAs further led to a successive decline in JrGA20ox1 expression and active GA content. Meanwhile, unknown mobile signals may move between rootstocks and scions. These mobile signals reduced the expression of a series of GA-responsive and GA-non-responsive genes, and induced ROS production in guard cells and an increase in ABA content, which may contribute to the drought tolerance of WT/RNAi, while the opposite occurred in WT/OE. The findings suggest that JrGA20ox1-derived rootstock-to-scion movement of signals is involved in drought tolerance of scions. Our research will provide a feasible approach for studying signal communication in woody plants.
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OBJECTIVES: Thoracic surgery is a complex field requiring advanced technical skills and critical decision-making. Surgical education must evolve to equip trainees with proficiency in new techniques and technologies. METHODS: This bibliometric analysis systematically reviewed 113 articles on thoracic surgery skills training published over the past decade, retrieved from databases including Web of Science. Publication trends, citation analysis, author and journal productivity, and keyword frequencies were evaluated. RESULTS: The United States contributed the most publications, led by pioneering institutions. Simulation training progressed from basic to sophisticated modalities and virtual reality emerged with transformative potential. Minimally invasive techniques posed unique learning challenges requiring integrated curricula. CONCLUSION: Ongoing investments in educational research and curriculum innovations are imperative to advance thoracic surgery training through multidisciplinary strategies. This study provides an evidentiary foundation to optimize training and address the complexities of modern thoracic surgery.
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Bibliometría , Cirugía Torácica , Humanos , Competencia Clínica , Curriculum , Cirugía Torácica/educación , Procedimientos Quirúrgicos Torácicos/educaciónRESUMEN
Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly tumors; however, its pathogenic mechanism remains largely elusive. In-depth researches are needed to reveal the expression regulatory mechanisms and functions of the RNA-binding protein RALY in HCC. Here, we identify RALY as a highly expressed oncogenic factor that affects HCC cells proliferation both in vitro and in vivo. O-GlcNAcylation of RALY at Ser176 enhances its stability by protecting RALY from TRIM27-mediated ubiquitination, thus maintaining hyper-expression of the RALY protein. Mechanistically, RALY interacts with USP22 messenger RNA, as revealed by RNA immunoprecipitation, to increase their cytoplasmic localization and protein expression, thereby promoting the proliferation of HCC cells. Furthermore, we develop a novel RALY protein degrader based on peptide proteolysis-targeting chimeras, named RALY-PROTAC, which we chemically synthesize by linking a RALY-targeting peptide with the E3 ubiquitin ligase recruitment ligand pomalidomide. In conclusion, our findings demonstrate a novel mechanism by which O-GlcNAcylation/RALY/USP22 mRNA axis aggravates HCC cells proliferation. RALY-PROTACs as degraders of the RALY protein exhibit potential as therapeutic drugs for RALY-overexpressing HCC.
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Carcinoma Hepatocelular , Proliferación Celular , Neoplasias Hepáticas , Ubiquitina Tiolesterasa , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Línea Celular Tumoral , Animales , ARN Mensajero/metabolismo , ARN Mensajero/genética , Ratones , Ratones Desnudos , Ubiquitinación , Transporte Activo de Núcleo CelularRESUMEN
Rational design of small organic molecule-based NIR-II photosensitizers (PSs) with high singlet oxygen quantum yield in aqueous solution for deep tissue imaging and cancer therapy still presents challenges. Herein, we devised a general synthesis strategy to obtain six NIR-II region PSs with tunable aggregation states by adjusting the steric effect, and all PSs possess longer NIR absorption/emission wavelengths with tails extending beyond 1200 nm. Notably, ATX-6 possessed a singlet oxygen quantum yield of 38.2% and exhibited concentration-dependent J-aggregation properties upon self-assembly in an aqueous solution. What's more, supramolecular engineering with DSPE-PEG2000 further enhanced its degree of J-aggregation, which was attributed to the dimer-excited reduction of the energy levels of the single-linear/triple-linear states and the facilitation of intersystem crossover processes. In addition, ATX-6 NPs showed superior photodynamic therapy effects and great potential in high-contrast in vivo bioimaging of the NIR-II region. These results provide valuable insights for achieving the diagnostic and therapeutic integration of tumors.
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Urethral stricture (US) is a challenging problem in urology and its pathogenesis of US is closely related to the fibrotic process. Previous evidence has indicated the downregulation of microRNA (miR)-486 in injured urethral specimens of rats. This study aimed to explore the effects of miR-486-overexpressed bone marrow mesenchymal stem cells (BMSCs) on US. BMSCs were identified by detecting their multipotency and surface antigens. Lentivirus virus expressing miR-486 was transduced into rat BMSCs to overexpress miR-486. Transforming growth factor (TGF)-ß1 induced fibrotic phenotypes in urethral fibroblasts (UFs) and rat models. Western blotting showed protein levels of collagen I/III and collagen type XIII alpha 1 chain (Col13a1). Real time quantitative polymerase chain reaction was utilized for messenger RNA level evaluation. Hematoxylin-eosin, Masson's trichrome, and Von Willebrand Factor staining were conducted for histopathological analysis. Immunofluorescence staining was employed for detecting alpha smooth muscle actin (α-SMA) expression. Luciferase reporter assay verified the interaction between miR-486 and Col13a1. The results showed that miR-486-overexpressed BMSCs suppressed collagen I/III and α-SMA expression in TGF-ß1-stimulated UFs. miR-486-overexpressed BMSCs alleviated urethral fibrosis, collagen deposition, and epithelial injury in the urethral tissue of US rats. miR-486 targeted and negatively regulated Col13a1 in US rats. In conclusion, overexpression of miR-486 in BMSCs targets Col13a1 and attenuates urethral fibrosis in TGF-ß1-triggered UFs and US rats.
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In planta expression of recombinant antibodies has been proposed as a strategy for herbicide resistance but is not well advanced yet. Here, an atrazine nanobody gene fused with a green fluorescent protein tag was transformed to Arabidopsis thaliana, which was confirmed with PCR, ELISA, and immunoblotting. High levels of nanobody accumulation were observed in the nucleus, cytoderm, and cytosol. The nanobody expressed in the plant had similar affinity, sensitivity, and selectivity as that expressed in Escherichia coli. The T3 homozygous line showed resistance in a dose-dependent manner up to 380 g ai/ha of atrazine, which is approximately one-third of the recommended field application rate. This is the first report of utilizing a nanobody in plants against herbicides. The results suggest that utilizing a high-affinity herbicide nanobody gene rather than increasing the expression of nanobodies in plants may be a technically viable approach to acquire commercial herbicide-resistant crops and could be a useful tool to study plant physiology.
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Arabidopsis , Atrazina , Resistencia a los Herbicidas , Herbicidas , Plantas Modificadas Genéticamente , Anticuerpos de Dominio Único , Atrazina/farmacología , Herbicidas/farmacología , Arabidopsis/genética , Arabidopsis/inmunología , Arabidopsis/metabolismo , Arabidopsis/efectos de los fármacos , Resistencia a los Herbicidas/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/inmunología , Anticuerpos de Dominio Único/genética , Anticuerpos de Dominio Único/farmacología , Anticuerpos de Dominio Único/inmunologíaRESUMEN
Despite their crucial role in determining the fate of seeds, the type and breaking mode of seed dormancy in peatland plants in temperate Asia with a continental monsoon climate are rarely known. Fifteen common peatland plant species were used to test their seed germination response to various dormancy-breaking treatments, including dry storage (D), gibberellin acid soaking (GA), cold stratification (CS), warm followed cold stratification (WCS), GA soaking + cold stratification (GA + CS) and GA soaking + warm followed cold stratification (GA + WCS). Germination experiment, viability and imbibition test, and morphological observation of embryos were conducted. Of the 15 species, nine showed physiological dormancy (PD), with non-deep PD being the dominant type. Four species, Angelica pubescens, Cicuta virosa, Iris laevigata, and Iris setosa exhibited morphophysiological dormancy. Two species, Lycopus uniflorus and Spiraea salicifolia, demonstrated nondormancy. Overall, the effect hierarchy of dormancy-breaking is: CS > GA > WCS > GA + CS > D > GA + WCS. Principal component analysis demonstrated that seed traits, including embryo length: seed length ratio, seed size, and monocot/eudicot divergence, are more likely to influence seed dormancy than environmental factors. Our study suggests that nearly 90% of the tested peatland plant species in the Changbai Mountains demonstrated seed dormancy, and seed traits (e.g. embryo-to-seed ratio and seed size) and abiotic environmental factors (e.g. pH and temperature seasonality) are related to germination behavior, suggesting seed dormancy being a common adaptation strategy for the peatland plants in the temperate montane environment.
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Methamphetamine (MA) is a neurological drug, which is harmful to the overall brain cognitive function when abused. Based on this property of MA, people can be divided into those with MA abuse and healthy people. However, few studies to date have investigated automatic detection of MA abusers based on the neural activity. For this reason, the purpose of this research was to investigate the difference in the neural activity between MA abusers and healthy persons and accordingly discriminate MA abusers. First, we performed event-related potential (ERP) analysis to determine the time range of P300. Then, the wavelet coefficients of the P300 component were extracted as the main features, along with the time and frequency domain features within the selected P300 range to classify. To optimize the feature set, F_score was used to remove features below the average score. Finally, a Bidirectional Long Short-term Memory (BiLSTM) network was performed for classification. The experimental result showed that the detection accuracy of BiLSTM could reach 83.85%. In conclusion, the P300 component of EEG signals of MA abusers is different from that in normal persons. Based on this difference, this study proposes a novel way for the prevention and diagnosis of MA abuse.
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PURPOSE: This study evaluates the influence of spinal malalignment on health-related quality of life (HRQOL) in a long-level fusion spine. METHODS: This was a retrospective analysis of 121 consecutive patients with DLS after long-segment fusion. HRQOL and radiographic parameters were collected at final follow-up. For postoperative residual Cobb angle (CA), patients were divided as follows: group (0) (CA < 10°), group (+) (CA 10°â¼20 °), and group (++) (CA > 20°). For postoperative coronal vertical axis (CVA), patients were separated as follows: group (0) (CVA < 2 cm), group (+) (CVA 2 â¼ 3 cm), and group (++) (CVA > 3 cm). Patients were also grouped by the sagittal modifiers as group (0), group (+), and group (++) according to the Scoliosis Research Society (SRS)-Schwab classification, respectively. RESULTS: Visual analog scale (VAS) for back was significantly lower in CA 10°â¼20° group compared to other groups. Patients with remnant CA > 20° showed worse Oswestry Disability Index (ODI), SRS-22 and the 36-item Short Form Health Survey (SF-36) - physical component scores (PCS). Sagittal vertical axis (SVA) showed significant correlation with HRQOLs after surgery, and the statistical significance of ODI, SRS-22 and SF-36 scores was observed among subgroups. CONCLUSIONS: In long-level fused spine, residual CA > 20° resulted in worse clinical outcomes and was recommended to avoid during surgery. And 10° to 20° residual CA was acceptable in DLS patients and even better than Cobb angle < 10° in several HRQOLs, therefore strictly pursing upright alignment seems unnecessary. SVA also showed effectiveness in assessing HRQOL in the fixed spine.
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Disentangling the limitations of O-O bond activation and OH* site-blocking effects on Pt sites is key to improving the intrinsic activity and stability of low-Pt catalysts for the oxygen reduction reaction (ORR). Herein, we integrate of PtFe alloy nanocrystals on a single-atom Fe-N-C substrate (PtFe@FeSAs-N-C) and further construct a ferromagnetic platform to investigate the regulation behavior of the spin occupancy state of the Pt d-orbital in the ORR. PtFe@FeSAs-N-C delivers a mass activity of 0.75 A mgPt-1 at 0.9 V and a peak power density of 1240 mW cm-2 in the fuel-cell, outperforming the commercial Pt/C catalyst, and a mass activity retention of 97%, with no noticeable current drop at 0.6 V for more than 220 h, is attained. Operando spectroelectrochemistry decodes the orbital interaction mechanism between the active center and reaction intermediates. The Pt dz2 orbital occupation state is regulated to t2g6eg3 by spin-charge injection, suppressing the OH* site-blocking effect and effectively inhibiting H2O2 production. This work provides valuable insights into designing high-performance and low-Pt catalysts via spintronics-level engineering.