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Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32-1.87] and 40% (OR 1.40, 95% CI 1.19-1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40-0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.
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Lipídeos , Hepatopatia Gordurosa não Alcoólica , Ácido Úrico , Humanos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Masculino , Feminino , Ácido Úrico/sangue , Adulto , China/epidemiologia , Lipídeos/sangue , Pessoa de Meia-Idade , Fatores de Risco , Incidência , Índice de Massa CorporalRESUMO
The development of multifunctional coatings is a trend. Here, a conductive and superhydrophobic coating with nest-like structure was prepared on the wood or polyurethane (PU) sponge by spraying or soaking methods. The coating contains lignin and carboxylated multi-wall carbon nanotubes (MWCNT) as the main materials, both methyl trimethoxysilane (MTMS) and polydimethylsiloxane (PDMS) as the modifiers. And benefiting from the protective effect of the nest-like structure, the coating exhibits excellent abrasion resistance (withstanding 43 abrasion cycles), stability, and UV resistance (little change in water contact angle after 240 h of ultraviolet (UV) irradiation) by optimizing the proportions. Additionally, the coating provides eminent deicing (complete removal after 142.7 s) and self-cleaning on the wood, as well as the superior sensing performance and oil absorption (15.0-49.6 g/g for various oils) on the PU sponge. When assembled into compressible piezoresistive sensor, it could clearly sense the signals of rapid, short, circulation, different speed and deformation, possessing a prosperous wearable device prospect. It is envisaged that the coating supplies a new platform for superhydrophobicity, wearable electronics and oil absorption.
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Due to their exceptional adaptability, inherent compliance, and high flexibility, soft actuators have significant advantages over traditional rigid actuators in human-machine interaction and in grasping irregular or fragile objects. Most existing soft actuators are designed using preprogramming methods, which schedule complex motions into flexible structures by correctly designing deformation constraints. These constraints restrict undesired deformation, allowing the actuator to achieve the preprogrammed motion when stimulated. Therefore, these actuators can only achieve a certain type of motion, such as extension, bending, or twisting, since it is impossible to adjust the deformation constraints once they are embedded into the structures. In this study, we propose the use of variable stiffness materials, such as shape memory polymer (SMP), in the structural design of soft actuators to achieve variable stiffness constraints. A reconfigurable soft helical actuator with a variable stiffness skeleton is developed based on this concept. The skeleton, made of SMP, is encased at the bottom of a fiber-reinforced chamber. In its high-stiffness state, the SMP constrains the deformation toward the skeleton when the actuator is pressurized. This constraint is removed once the SMP skeleton is heated, endowing the actuator with the ability to switch between bending and helical motion in real-time. A theoretical model is proposed to predict the behavior of the actuator when driven by pressure, and experiments are conducted to verify the model's accuracy. In addition, the influence of different design parameters is investigated based on experimental results, providing reference guidelines for the design of the actuator.
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Water electrolysis assisted by hydrazine has emerged as a prospective energy conversion method for achieving efficient hydrogen generation. Due to the potential coincidence region (PCR) between the hydrogen evolution reaction (HER) and the electro-oxidation of hydrazine, the hydrazine oxidation reaction (HzOR) offers distinct advantages in terms of strategy amalgamation, device architecture, and the broadening of application horizons. Herein, we report a bifunctional electrocatalyst of interfacial heterogeneous Fe2P/Co2P microspheres supported on Ni foam (FeCoP/NF). Benefiting from the strong interfacial coupling effect between Fe2P and Co2P and the three-dimensional microsphere structure, FeCoP/NF exhibits outstanding bifunctional electrocatalytic performance, achieving 10 mA cm-2 with low overpotentials of 10 and 203 mV for HER and HzOR, respectively. Utilizing FeCoP/NF for both electrodes in HzOR-assisted water electrolysis results in significantly reduced potentials of 820 mV for 1 A cm-2 in contrast to the electro-oxidation of alternative chemical substrates. The presence of a potential coincidence region makes the application of self-activated seawater electrolysis realistic. The gas production behavior at different current densities in this interesting hydrogen production system is discussed, and some rules that are distinguished from conventional water electrolysis are summarized. Furthermore, a new self-powered hydrogen production system with a direct hydrazine fuel cell, rechargeable Zn-hydrazine battery, and hydrazine-assisted seawater electrolysis is proposed, emphasizing the distinct benefits of HzOR and its potential role in electrochemical energy conversion technologies powered by renewable sources.
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Purpose: To examine the effects of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) on choroidal structures with different blood glucose levels in patients with diabetes mellitus (DM) with acromegaly without diabetic retinopathy. Methods: Eighty-eight eyes of 44 patients with acromegaly were divided into a nondiabetic group (23 patients, 46 eyes) and a diabetic group (21 patients, 42 eyes). Forty-four age- and sex-matched healthy controls and 21 patients with type 2 DM without diabetic retinopathy were also included. Linear regression models with a simple slope analysis were used to identify the correlation and interaction between endocrine parameters and choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascular index (CVI). Results: Our study revealed significant increases in the ChT, LA, SA, and TCA in patients with acromegaly compared with healthy controls, with no difference in the CVI. Comparatively, patients with DM with acromegaly had greater ChT than matched patients with type 2 DM, with no significant differences in other choroidal parameters. The enhancement of SA, LA and TCA caused by an acromegalic status disappeared in patients with diabetic status, whereas ChT and CVI were not affected by the interaction. In the diabetic acromegaly, higher IGF-1 (P = 0.006) and GH levels (P = 0.049), longer DM duration (P = 0.007), lower blood glucose (P = 0.001), and the interaction between GH and blood glucose were associated independently with thicker ChT. Higher GH levels (P = 0.016, 0.004 and 0.007), longer DM duration (P = 0.022, 0.013 and 0.013), lower blood glucose (P = 0.034, 0.011 and 0.01), and the interaction of IGF-1 and blood glucose were associated independently with larger SA, LA, and TCA. As blood glucose levels increased, the positive correlation between serum GH level and ChT diminished, and became insignificant when blood glucose was more than 7.35 mM/L. The associations between serum IGF-1 levels and LA, SA, and TCA became increasingly negative, with LA, becoming significantly and negatively associated to the GH levels only when blood glucose levels were more than 8.59 mM/L. Conclusions: Acromegaly-related choroidal enhancements diminish in the presence of DM. In diabetic acromegaly, blood glucose levels are linked negatively with changes in choroidal metrics and their association with GH and IGF-1. Translational Relevance: We revealed the potential beneficial impacts of IGF-1 and GH on structural measures of the choroid in patients with DM at relatively well-controlled blood glucose level, which could provide a potential treatment target for diabetic retinopathy.
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Acromegalia , Glicemia , Corioide , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Fator de Crescimento Insulin-Like I , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/análise , Acromegalia/sangue , Acromegalia/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Corioide/patologia , Glicemia/análise , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/sangue , Adulto , Idoso , Tomografia de Coerência Óptica , Hormônio do Crescimento Humano/sangue , Estudos de Casos e ControlesRESUMO
The exploration and advancement of highly efficient anode materials for lithium-ion batteries (LIBs) are critical to meet the growing demands of the energy storage market. In this study, we present an easily scalable synthesis method for the one-pot formation of few-layer MoS2 nanosheets on a N,S dual-doped carbon monolith with a two-dimensional (2D) architecture, termed MoS2/NSCS. Systematic electrochemical measurements demonstrate that MoS2/NSCS, when employed as the anode material in LIBs, exhibits a high capacity of 681 mA h g-1 at 0.2 A g-1 even after 110 cycles. The exceptional electrochemical performance of MoS2/NSCS can be attributed to its unique porous 2D architecture. The few-layer MoS2 sheets with a large interlayer distance reduce ion diffusion pathways and enhance ion mobility rates. Additionally, the N,S-doped porous carbon matrix not only preserves structural integrity but also facilitates electronic conductivity. These combined factors contribute to the reversible electrochemical activities observed in MoS2/NSCS, highlighting its potential as a promising anode material for high-performance LIBs.
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BACKGROUND: Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. METHODS: The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. RESULTS: 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p < 0.05). High-order aberrations decreased significantly (p < 0.05). Despite the high incidence of posterior capsule opacification (83.2%), managed with early Nd: YAG capsulotomy, no other severe complications were reported. Patient-reported outcomes indicated high satisfaction, with an average VF-14 score of 94.3 ± 10.2 and 93.5% achieving complete spectacle independence. Halo (66.2%) was the most commonly reported optical phenomena, followed by glare (18.2%), and starburst (7.8%) after surgery. CONCLUSIONS: Bilateral RLE with trifocal IOLs in presbyopic patients without cataracts significantly improves visual acuity and reduces ocular aberrations in presbyopic patients. The procedure offers high patient satisfaction and spectacle independence, though it requires careful patient selection and management of expectations regarding potential photic phenomena.
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Implante de Lente Intraocular , Lentes Intraoculares Multifocais , Satisfação do Paciente , Presbiopia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , População do Leste Asiático , Implante de Lente Intraocular/métodos , Presbiopia/cirurgia , Presbiopia/fisiopatologia , Refração Ocular , Inquéritos e Questionários , Visão Binocular , Acuidade VisualRESUMO
ABSTRACT: Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the brain, defects in y-aminobutyric acid (GABA) synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 (GLP-1) has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to RGCs and whether and how GLP-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to RGCs. In the present study, we used the patch-clamp technique to record GABA subtype A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in RGCs from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic mIPSCs in RGCs without altering their amplitude, suggesting a reduction in the spontaneous release of GABA to RGCs. Topical administration of GLP-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of RGCs. Concurrently, the protective effects of GLP-1 on RGCs in diabetic rats were eliminated by topical administration of exendin-9-39, a specific GLP-1 receptor antagonist, or SR95531, a specific antagonist of the GABA subtype A receptor. Furthermore, extracellular perfusion of GLP-1 was found to elevate the frequencies of GABAergic mIPSCs in both ON- and OFF-type RGCs. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of GLP-1 receptor activation. Moreover, multielectrode array recordings revealed that GLP-1 functionally augmented the photoresponses of ON-type RGCs. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of GLP-1. These results suggest that GLP-1 facilitates the release of GABA onto RGCs through the activation of GLP-1 receptor, leading to the de-excitation of RGC circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the GABA system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of GLP-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
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BACKGROUND: Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast. RESULTS: Here through Atmospheric and Room Temperature Plasma (ARTP)-based mutagenesis and transcriptomic analysis, the expression of two genes MYO1 and IQG1 encoding the cytokinesis core proteins was identified downregulated along with higher hLYZ production. Deletion of either gene caused severe cytokinesis defects, but significantly enhanced hLYZ production. The highest hLYZ yield of 1,052,444 ± 23,667 U/mL bioactivity and 4.12 ± 0.11 g/L total protein concentration were obtained after high-density fed-batch fermentation in the Δmyo1 mutant, representing the best production of hLYZ in yeast. Furthermore, O-linked mannose glycans were characterized on this recombinant hLYZ. CONCLUSIONS: Our work suggests that cytokinesis-based morphology engineering is an effective way to enhance the production of hLYZ in K. phaffii.
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Muramidase , Proteínas Recombinantes , Saccharomycetales , Muramidase/metabolismo , Muramidase/genética , Muramidase/biossíntese , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomycetales/metabolismo , Saccharomycetales/genética , Humanos , Fermentação , Citocinese , Engenharia Metabólica/métodos , Técnicas de Cultura Celular por LotesRESUMO
This article designs and implements a fast and high-precision multi-robot environment modeling method based on bidirectional filtering and scene identification. To solve the problem of feature tracking failure caused by large angle rotation, a bidirectional filtering mechanism is introduced to improve the error-matching elimination algorithm. A global key frame database for multiple robots is proposed based on a pretraining dictionary to convert images into a bag of words vectors. The images captured by different sub-robots are compared with the database for similarity score calculation, so as to realize fast identification and search of similar scenes. The coordinate transformation from local map to global map and the cooperative SLAM exploration of multiple robots is completed by the best matching image and the transformation matrix. The experimental results show that the proposed algorithm can effectively close the predicted trajectory of the sub-robot, thus achieving high-precision collaborative environment modeling.
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BACKGROUND: Thyroid eye disease (TED) is an inflammatory process involving lymphocyte-mediated immune response and orbital tissue damage. The anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies produced by B lymphocytes are involved in the activation of orbital fibroblasts and the inflammatory process of orbital tissue damage in TED. The purpose of this study was to explore the role of IGF-1R in the mechanistic connection between orbital fibroblasts and B lymphocytes in TED. METHODS: Orbital fibroblasts sampled from orbital connective tissues and peripheral B lymphocytes isolated from peripheral blood, which were obtained from 15 patients with TED and 15 control patients, were co-cultured at a ratio of 1:20. The level of IGF-1R expression in orbital fibroblasts was evaluated by flow cytometry and confocal microscopy. Transient B lymphocyte depletion was induced with anti-CD20 monoclonal antibody rituximab, while the IGF-1R pathway was blocked by the IGF-1R binding protein. The expression levels of interleukin-6 (IL-6) and regulated upon activation, normal T cell expressed and secreted (RANTES) in the co-culture model were quantified via ELISA. RESULTS: IGF-1R expression was significantly elevated in TED orbital fibroblasts compared to that of controls. A 24-h co-culture of orbital fibroblasts with peripheral B lymphocytes induced elevated expression levels of IL-6 and RANTES in each group (TED patients and controls), with the highest levels occurring in TED patients (T + T group). Rituximab and IGF-1R binding protein significantly inhibited increased levels of IL-6 and RANTES in the co-culture model of TED patients. CONCLUSIONS: IGF-1R may mediate interaction between orbital fibroblasts and peripheral B lymphocytes; thus, blocking IGF-1R may reduce the local inflammatory response in TED. Rituximab-mediated B lymphocyte depletion played a role in inhibiting inflammatory responses in this in vitro co-culture model, providing a theoretical basis for the clinical application of anti-CD20 monoclonal antibodies in TED.
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Linfócitos B , Fibroblastos , Oftalmopatia de Graves , Receptor IGF Tipo 1 , Feminino , Humanos , Masculino , Linfócitos B/imunologia , Linfócitos B/metabolismo , Comunicação Celular , Células Cultivadas , Quimiocina CCL5/metabolismo , Técnicas de Cocultura , Fibroblastos/metabolismo , Oftalmopatia de Graves/metabolismo , Oftalmopatia de Graves/imunologia , Interleucina-6/metabolismo , Depleção Linfocítica , Órbita/metabolismo , Órbita/imunologia , Receptor IGF Tipo 1/metabolismo , Rituximab/farmacologia , Rituximab/uso terapêuticoRESUMO
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients' clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the "dominant" phenotype in idiopathic double-positive AAV.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Mieloblastina , Prognóstico , Peroxidase , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , RecidivaRESUMO
In contrast to the thermodynamically unfavorable anodic oxygen evolution reaction, the electrocatalytic urea oxidation reaction (UOR) presents a more favorable thermodynamic potential. However, the practical application of UOR has been hindered by sluggish kinetics. In this study, hierarchical porous nanosheet arrays featuring abundant Ni-WO3 heterointerfaces on nickel foam (Ni-WO3/NF) is introduced as a monolith electrode, demonstrating exceptional activity and stability toward UOR. The Ni-WO3/NF catalyst exhibits unprecedentedly rapid UOR kinetics (200 mA cm-2 at 1.384 V vs. RHE) and a high turnover frequency (0.456 s-1), surpassing most previously reported Ni-based catalysts, with negligible activity decay observed during a durability test lasting 150 h. Ex situ X-ray photoelectron spectroscopy and density functional theory calculations elucidate that the WO3 interface significantly modulates the local charge distribution of Ni species, facilitating the generation of Ni3+ with optimal affinity for interacting with urea molecules and CO2 intermediates at heterointerfaces during UOR. This mechanism accelerates the interfacial electrocatalytic kinetics. Additionally, in situ Fourier transform infrared spectroscopy provides deep insights into the substantial contribution of interfacial Ni-WO3 sites to UOR electrocatalysis, unraveling the underlying molecular-level mechanisms. Finally, the study explores the application of a direct urea fuel cell to inspire future practical implementations.
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Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.
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Tunability of interfacial effects between two-dimensional (2D) crystals is crucial not only for understanding the intrinsic properties of each system, but also for designing electronic devices based on ultra-thin heterostructures. A prerequisite of such heterostructure engineering is the availability of 2D crystals with different degrees of interfacial interactions. In this work, we report a controlled epitaxial growth of monolayer TaSe2 with different structural phases, 1H and 1 T, on a bilayer graphene (BLG) substrate using molecular beam epitaxy, and its impact on the electronic properties of the heterostructures using angle-resolved photoemission spectroscopy. 1H-TaSe2 exhibits significant charge transfer and band hybridization at the interface, whereas 1 T-TaSe2 shows weak interactions with the substrate. The distinct interfacial interactions are attributed to the dual effects from the differences of the work functions as well as the relative interlayer distance between TaSe2 films and BLG substrate. The method demonstrated here provides a viable route towards interface engineering in a variety of transition-metal dichalcogenides that can be applied to future nano-devices with designed electronic properties.
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This paper designed and developed an online digital imaging excitation sensor for wind power gearbox wear condition monitoring based on an adaptive deep learning method. A digital imaging excitation sensing image information collection architecture for magnetic particles in lubricating oil was established to characterize the wear condition of mechanical equipment, achieving the real-time online collection of wear particles in lubricating oil. On this basis, a mechanical equipment wear condition diagnosis method based on online wear particle images is proposed, obtaining data from an engineering test platform based on a wind power gearbox. Firstly, a foreground segmentation preprocessing method based on the U-Net network can effectively eliminate the interference of bubbles and dark fields in online wear particle images, providing high-quality segmentation results for subsequent image processing, A total of 1960 wear particle images were collected in the experiment, the average intersection union ratio of the validation set is 0.9299, and the accuracy of the validation set is 0.9799. Secondly, based on the foreground segmentation preprocessing of wear particle images, by using the watered algorithm to obtain the number of particles in each size segment, we obtained the number of magnetic particle grades in three different ranges: 4-38 µm, 39-70 µm, and >70 µm. Thirdly, we proposed a method named multidimensional transformer (MTF) network. Mean Square Error (MSE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE) are used to obtain the error, and the maintenance strategy is formulated according to the predicted trend. The experimental results show that the predictive performance of our proposed model is better than that of LSTM and TCN. Finally, the online real-time monitoring system triggered three alarms, and at the same time, our offline sampling data analysis was conducted, the accuracy of online real-time monitoring alarms was verified, and the gearbox of the wind turbine was shut down for maintenance and repair.
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Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal-organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu2+) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu2+ was reduced to Cu+ by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H2O2) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.
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Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Humanos , Cobre , Estruturas Metalorgânicas/farmacologia , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Estudos Prospectivos , Glutationa , Concentração de Íons de Hidrogênio , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
INTENTION: Immunosuppressive therapy is the major treatment approach for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Due to impaired cellular immunological function and the use of glucocorticoids and immunosuppressants, AAV patients are predisposed to opportunistic infections, including tuberculosis (TB). This retrospective study aims to analyze the clinical characteristics of patients with AAV and TB and explore suitable glucocorticoid regimens for them. So as to provide a basis for future clinical guidelines and have important value for guiding clinical treatment. METHODS: This study retrospectively reviewed 58 AAV patients (18-80 years old) with TB admitted to Changsha Central Hospital Affiliated with the University of South China from 2016.1 to 2023.4 Patients were divided into standard-dose and reduced-dose glucocorticoid groups before retrospectively analyzing their medical records. RESULTS: A total of 58 AAV patients with TB were enrolled, with 15 dying throughout the monitoring period. Through analysis data, compared with the standard-dose group, the reduced group had less proteinuria and hematuria. In survival analysis, the reduced-dose glucocorticoid group had lower mortality than the standard-dose group (P = 0.03); however, no significant difference was noted in the use of immunoglobulin (P = 0.39), tuberculosis activity (P = 0.64), and age stratification (P = 0.40). The BVAS score before treatment and 6 months post-treatment suggest that the two regimens cause the same risk of ESKD (P > 0.05). CONCLUSION: In conclusion, the reduced glucocorticoid dose group can achieve the same curative effect as the standard dose group and has less damage to the kidney in hematuria and proteinuria. Therefore, the reduced glucocorticoid dose treatment regimen may be more suitable for AAV patients with TB.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glucocorticoides , Tuberculose , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Masculino , Feminino , Idoso , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Adulto Jovem , Idoso de 80 Anos ou mais , Adolescente , Tuberculose/tratamento farmacológico , Tuberculose/complicações , China , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêuticoRESUMO
PURPOSE: To assess the retinal structural and microvascular change in aquaporin-4 antibody (AQP4) positive neuromyelitis optica spectrum disorder (NMOSD) patients and the correlation with clinical features. METHODS: A cross-sectional study was performed with optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to measure retinal structure and microvascular parameters in AQP4 positive NMOSD patients. RESULTS: Sixty-two NMOSD patients (44 eyes with ON, NMOSD+ON; 77 eyes without ON, NMOSD-ON) and 62 healthy controls (HC, 124 eyes) were included. BCVA was worse in NMOSD patients compared to HC (p<0.001). Peripapillary retinal nerve fiber layer (pRNFL, p<0.001) and ganglion cell complex (GCC, p<0.001) was thinner in NMOSD+ON eyes compared to NMOSD-ON eyes and HC. Compared to HC, pRNFL (p = 0.002) and GCC (p = 0.001) was thinner in NMOSD-ON eyes. The vessel density (VD) in superficial capillary plexus (SCP, NMOSD+ON vs HC p<0.001, NMOSD-ON vs HC p = 0.002) and radial peripapillary capillary (RPC, NMOSD+ON vs HC p<0.001, NMOSD-ON vs HC p = 0.001) were also lower in NMOSD patients than HC independent of the history of ON. ON frequency and BCVA were correlated with the thickness of pRNFL and GCC, and VD in SCP and RPC (all p<0.001). EDSS was correlated with thickness of GCC (p = 0.008), and VD in SCP (p = 0.013), DCP (p<0.001) and RPC (p = 0.009). CONCLUSIONS: Subclinical degradation of retinal structure and microvasculature was found in NMOSD patients before the occurrence of ON, and was correlated with clinical disability. Retinal parameter might be a tool to estimate the disease progression and investigate the pathogenesis of NMOSD.