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ETHNOPHARMACOLOGICAL RELEVANCE: Our previous studies have shown that the Qingre Qushi (QRQS) formula can treat atopic dermatitis (AD), and its possible mechanism is related to the regulation of the IL-33/ST2 signaling pathway. However, the molecular mechanism of AD is complex, and various AD subtypes respond better to therapies aimed at distinct targets. AIM OF THE STUDY: This study aimed to investigate the multi-target mechanism of QRQS using experimental and network pharmacology studies. MATERIALS AND METHODS: Flaky tail (FT) mice were treated with different concentrations of QRQS and cetirizine. The dermatitis score, scratching frequency, and histological evaluation were normatively evaluated. The levels of IgE and IgG1 in serum were tested using ELISAs. Using ELISA and RT-PCR, the expression of associated cytokines was determined. IL-17A-stimulated HaCaT cells were treated with QRQS to assess mRNA and protein expression. To elucidate the mechanism, a network pharmacology analysis based on active components derived from UPLC was conducted. Through molecular docking, we evaluated the binding affinity between the active constituents of QRQS and potential targets. RESULTS: Using UPLC, 177 active ingredients in QRQS were identified. Network pharmacology analysis showed that the anti-AD effect of the active ingredients was related to the IL-17 signaling pathway and its related targets. FT mice are characterized by Th17-dominated immune disorders. QRQS ameliorated AD-like symptoms and decreased dermatitis scores and scratching frequencies. After QRQS treatment, IL-17A expression was inhibited and IL-17 pathway-associated cytokines were downregulated. Along with changes in Th17-differentiation, QRQS suppressed the expression of IL-4, IL-13, and TNF-α. QRQS also decreased the expression of IL-6, IL-8, and COX-2 in HaCaT cells exposed to IL-17A. The anti-AD active doses are 3.86 g/kg/day in vivo and 100 µg/mL in vitro. CONCLUSION: QRQS has a multi-target immunoregulatory effect on AD and can improve the Th17-dominated inflammatory response by regulating the IL-17A signaling pathway. Quercetin, genistein, luteolin, and kaempferol are potential active ingredients.
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Dermatite Atópica , Camundongos , Animais , Dermatite Atópica/patologia , Interleucina-17 , Simulação de Acoplamento Molecular , Imunoglobulina E , Citocinas/metabolismoRESUMO
The design of non-buckling interconnects with thick sections has gained important applications in stretchable inorganic electronics due to their simultaneous achievement of high stretchability, low resistance, and low heat generation. However, at the same time, such a design sharply increased the tensile stiffness, which is detrimental to the conformal fit and skin comfort. Introducing the fractal design into the non-buckling interconnects is a promising approach to greatly reduce the tensile stiffness while maintaining other excellent performances. Here, a hierarchical theory is proposed for the tensile stiffness of the non-buckling fractal-inspired interconnects with an arbitrary shape at each order, which is verified by the finite element analysis. The results show that the tensile stiffness of the non-buckling fractal-inspired interconnects decreases with the increase in either the height/span ratio or the number of fractal orders but is not highly correlated with the ratio of the two adjacent dimensions. When the ratio of the two adjacent dimensions and height/span ratio are fixed, the tensile stiffness of the serpentine fractal-inspired interconnect is smaller than that of sinusoidal and zigzag fractal-inspired interconnects. These findings are of great significance for the design of non-buckling fractal-inspired interconnects of stretchable inorganic electronics.
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The endosomal sorting complex required for transport (ESCRT) machinery is essential for the budding of retroviruses such as human immunodeficiency virus (HIV) and bovine foamy virus (BFV), which rely on their late domain to recruit ESCRT complexes to facilitate budding. However, the impact of intracellular host proteins on BFV budding remains poorly understood. In this study, we aimed to investigate the impact of CCL2 on BFV budding and interactions with key host proteins. Our results indicate that CCL2 promotes BFV budding in an ALG-2-interacting protein X (Alix)-dependent manner by enhancing the interaction between Alix and BFV Gag (BGag). Notably, we found a link between Alix, BGag and CCL2, with Alix mediating the interaction between the latter two. Furthermore, we observed that natural host bovine CCL2 also has a facilitating role in the budding process of BFV, similar to human CCL2. Taken together, these results demonstrate that CCL2 promotes BFV budding by enhancing the Alix-BGag association.
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Although the research on aqueous batteries employing metal as the anode is still mainly focused on the aqueous zinc-ion battery, aqueous iron-ion batteries are considered as promising aqueous batteries owing to the lower cost, higher specific capacity, and better stability. However, the sluggish Fe2+ (de)intercalation leads to unsatisfactory specific capacity and poor electrochemical stability, which makes it difficult to find cathode materials with excellent electrochemical properties. Herein, phenylamine (PA)-intercalated VOPO4 materials with expanded interlayer spacing are synthesized and applied successfully in aqueous iron-ion batteries. Owing to enough diffusion space from the expanded interlayer, which can boost fast Fe2+ diffusion, the aqueous iron-ion battery shows a high specific capacity of 170 mAh g-1 at 0.2 A g-1 , excellent rate performance, and cycle stability (96.2% capacity retention after 2200 cycles). This work provides a new direction for cathode material design in the development of aqueous iron-ion batteries.
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Extracellular vesicles bear a rich glycome that presents versatile functions in diverse biological processes. Leverage polydopamine modified magnetic particles to serve as nanosized agents for rapid and robust EV capture and manipulation, we here integrated the easy magnetic actuation with specific lectin-glycan binding and enzyme-mediated fluorescence amplification and thus proposed a facile approach to efficiently decipher a broad spectrum of glycans in EVs. Termed magnetic nanoagent assisted extracellular vesicle glycan deciphering (MAEG), the developed assay utilized a magnet as the assistant operation tool and realized fast (â¼1 h) and sensitive (a limit of detection of â¼0.7 µg/mL vesicles) EV glycan analysis in a simple low-cost (around 2.27 Chinese Yuan for one test) manner without requirement of any sophisticated platforms. With robust performance for different sample species, the assay achieved to depict the comprehensive glycosylation landscapes for varied EVs derived from eight cell lines focusing on non-small-cell lung cancer. Systematic analyses clearly revealed the high heterogeneity in glycan features of EVs of varied cellular origins. Using an established difference network method, unique glycan features in different EVs were sifted out and further compiled to construct lectin-denoted patterns as dedicated glycosylation fingerprints, potentially expanding EV-based clinical applications.
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PURPOSE: Abnormally increased epicardial fat appears to be associated with an additional risk of major adverse cardiovascular events (MACEs) in the context of metabolic syndrome (MetS). However, evidence on the relationship between epicardial fat volumes (EFVs), epicardial fat thickness (EFT) and MetS remains inconsistent. METHODS: Specific searches of electronic databases from 1 January 2000 to 31 October 2022 were independently performed by two researchers. In this study, two quantification measures of epicardial fat were included: comparison of total computed tomography-based EFVs and EFT between two groups (individuals with and without MetS), estimating standardized mean difference (SMD) with corresponding 95 % confidence intervals (CIs) through a random-effects model analysis. The heterogeneity in the included studies was explored by meta-regression and subgroup analyses. RESULTS: The EFVs were significantly increased in MetS subjects compared with non-MetS subjects (SMD: 1.07, 95 % CI: 0.69-1.45, p < 0.001), and the EFT was also significantly larger in MetS patients than in the Non-MetS (SMD: 1.12, 95 % CI: 0.84-1.41, p < 0.001). We compared the Caucasian and American subgroups with the Asian and African subgroups, and the EFT was greater in the former subgroups (SMD: 1.32, 95 % CI: 0.44-2.20, p < 0.001). When comparing the EFT among the age subgroups, there was a significant SMD between adolescents and adults or elderly individuals (SMD: 1.21, 95 % CI: 0.84-1.52, p < 0.001). CONCLUSIONS: MetS patients tend to present greater EFT near the right ventricular free wall and greater total EFVs. Increased epicardial fat, an imaging biomarker, independently affects the onset of MetS.
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Síndrome Metabólica , Adolescente , Adulto , Idoso , Humanos , Síndrome Metabólica/diagnóstico por imagem , Coração , Tecido Adiposo/diagnóstico por imagem , Bases de Dados Factuais , Tomografia Computadorizada por Raios XRESUMO
Therapeutic cancer nanovaccines can induce strong antitumor immunity and establish long-term immune memory and have shown potential for curing tumors in some clinical trials. However, weak immunogenicity and safety concerns of nanocarriers limit the clinical translation of some therapeutic nanovaccines. Here, we developed minimal-component cancer nanovaccines, monophosphoryl lipid A (MPLA)-assembled nanovaccines (MANs), that could facilitate the clinical application of nanovaccines. The MANs were formed by protein antigens extracted from chemotherapy-induced tumor cell cultures and the amphiphilic immune adjuvant MPLA. Compared with free chemotherapy-induced antigens, MANs can activate the Toll-like receptor 4 (TLR4)-mediated signalling pathway and promote adaptive immunity against tumor antigens. Mechanistic analysis indicated that MANs induced antigen capture of DCs and promoted the activation of DCs and T cells, thereby optimizing the ratio of CD8+ T/Tregs in tumors and facilitating the transformation of the tumor immune microenvironment (TIME) from "cold" to "hot". In a CT26 colorectal cancer model, MANs+αPD-1 significantly improved the efficacy of αPD-1 treatment. Our work offers a strategy for designing minimal-component cancer nanovaccines with potential clinical benefits. STATEMENT OF SIGNIFICANCE: To address the weak immunogenicity of cancer vaccines and the safety concerns of nanocarriers, we prepared MPLA-assembled nanovaccines (MANs) using chemotherapy induced antigens and the immune adjuvant MPLA to promote cancer vaccines to clinical practice. MANs effectively internalized tumor antigens and induced DC maturation, indicating that the initial anti-tumor response had been activated. MANs+αPD-1 induced APCs, CD8+ T cells and memory T cells with positive anti-tumor effects to migrate to tumor tissue, thus leading to the transformation of the tumor immune microenvironment from "cold" to "hot". At the animal level, the combination of MANs and αPD-1 exerted synergistic effects and significantly enhanced tumor immunotherapy. Therefore, the treatment regimen of MANs+αPD-1 has potential clinical benefits.
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BACKGROUND: Mutual help among members is critical to the accomplishment of complex tasks in an organization. Helping behaviors are infectious, and employees learn to imitate their coworkers' helping behaviors through observation. However, whether coworker helping triggers imitation learning depends on observers' motivational attributions for coworker helping behaviors to some extent. OBJECTIVE: Based on attribution theory and approach-avoidance framework, this research explored the approach and avoidance-oriented emotional and behavioral consequences of observers' prosocial and impression management motivational attributions of coworker helping behavior. METHODS: An experimental study with 178 participants and a field study with 259 employees was conducted. RESULTS: The results revealed that observers attribute coworkers' helpfulness to prosocial motivation, which elicited observers' approach-oriented emotions (i.e., positive empathy) and behaviors (i.e., helping behavior) and reduced coworker exclusion, while impression-management motivation elicited observers' avoidance-oriented emotions (i.e., disgust) and behaviors (i.e., coworker exclusion) and reduced helping behavior. CONCLUSION: The results suggest that prosocial motivational attributions and impression management motivational attributions are key factors in determining whether observers have approach- or avoidance-oriented emotions and behaviors toward coworker helping. Accordingly, individual employees and managers should focus on employees' motivation to help others in order to promote mutual support and harmony in the workplace.
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BACKGROUND: Deep brain stimulation (DBS) is commonly performed with patients awake to perform intraoperative microelectrode recordings and/or macrostimulation testing to guide final electrode placement. Supplemental information from atlas-based databases derived from prior patient data and visualised as efficacy heat maps transformed and overlaid onto preoperative MRIs can be used to guide preoperative target planning and intraoperative final positioning. Our quantitative analysis of intraoperative testing and corresponding changes made to final electrode positioning aims to highlight the value of intraoperative neurophysiological testing paired with image-based data to optimise final electrode positioning in a large patient cohort. METHODS: Data from 451 patients with movement disorders treated with 822 individual DBS leads at a single institution from 2011 to 2021 were included. Atlas-based data was used to guide surgical targeting. Intraoperative testing data and coordinate data were retrospectively obtained from a large patient database. Medical records were reviewed to obtain active contact usage and neurologist-defined outcomes at 1 year. RESULTS: Microelectrode recording firing profiles differ per track, per target and inform the locations where macrostimulation testing is performed. Macrostimulation performance correlates with the final electrode track chosen. Centroids of atlas-based efficacy heat maps per target were close in proximity to and may predict active contact usage at 1 year. Overall, patient outcomes at 1 year were improved for patients with better macrostimulation response. CONCLUSIONS: Atlas-based imaging data is beneficial for target planning and intraoperative guidance, and in conjunction with intraoperative neurophysiological testing during awake DBS can be used to individualize and optimise final electrode positioning, resulting in favourable outcomes.
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Oscillatory activity is thought to be a marker of cognitive processes, although its role and distribution across the brain during working memory has been a matter of debate. To understand how oscillatory activity differentiates tasks and brain areas in humans, we recorded local field potentials (LFPs) in 12 adults as they performed visual-spatial and shape-matching memory tasks. Tasks were designed to engage working memory processes at a range of delay intervals between stimulus delivery and response initiation. LFPs were recorded using intracranial depth electrodes implanted to localize seizures for management of intractable epilepsy. Task-related LFP power analyses revealed an extensive network of cortical regions that were activated during the presentation of visual stimuli and during their maintenance in working memory, including occipital, parietal, temporal, insular, and prefrontal cortical areas, and subcortical structures including the amygdala and hippocampus. Across most brain areas, the appearance of a stimulus produced broadband power increase, while gamma power was evident during the delay interval of the working memory task. Notable differences between areas included that occipital cortex was characterized by elevated power in the high gamma (100-150 Hz) range during the 500 ms of visual stimulus presentation, which was less pronounced or absent in other areas. A decrease in power centered in beta frequency (16-40 Hz) was also observed after the stimulus presentation, whose magnitude differed across areas. These results reveal the interplay of oscillatory activity across a broad network, and region-specific signatures of oscillatory processes associated with visual working memory.
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We developed an efficient MoS2 nanosheet electrode coupled with CeO2via a hydrothermal process to facilitate water adsorption and dissociation, which displayed good HER activity and stability at a large current density of 500 mA cm-2. In situ Raman spectroscopy confirmed the formation of hydroxide ions based on the strengthening of the Ce-O bond during the HER.
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BACKGROUND: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation. METHODS: Murine models of NSCLC with distinct driver mutations (KrasG12D/P53+/-/Lkb1-/- (KPL); KrasG12D/P53+/- (KP); and KrasG12D (K)) and varying tumor mutational burden were used to evaluate the efficacy of combination therapy with CCL21-DC ISV plus ICI. Comprehensive analyses of longitudinal preclinical samples by flow cytometry, single cell RNA-sequencing (scRNA-seq) and whole-exome sequencing were performed to assess mechanisms of combination therapy. RESULTS: ISV with CCL21-DC sensitized immune-resistant murine NSCLCs to ICI and led to the establishment of tumor-specific immune memory. Immunophenotyping revealed that CCL21-DC obliterated tumor-promoting neutrophils, promoted sustained infiltration of CD8 cytolytic and CD4 Th1 lymphocytes and enriched progenitor T cells in the TME. Addition of ICI to CCL21-DC further enhanced the expansion and effector function of T cells both locally and systemically. Longitudinal evaluation of tumor mutation profiles revealed that CCL21-DC plus ICI induced immunoediting of tumor subclones, consistent with the broadening of tumor-specific T cell responses. CONCLUSIONS: CCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras) , Proteína Supressora de Tumor p53 , Neoplasias Pulmonares/tratamento farmacológico , Imunoterapia , Microambiente Tumoral , Quimiocina CCL21RESUMO
Aging is a biological process that leads to the progressive deterioration and loss of physiological functions in the human body and results in an increase in morbidity and mortality, and aging-related disease is a major global problem that poses a serious threat to public health. Polysaccharides have been shown to delay aging by reducing oxidative damage, suppressing inflammatory responses, and modulating intestinal microbiota. Our previous studies have shown that polysaccharide CPP-1 extracted from the root of Codonopsis pilosula possesses noticeable anti-oxidant activity in vitro. Thus, in our study, we tested the anti-aging effect of CPP-1 in naturally aging mice (in vivo). Eighteen C57/BL mice (48-week-old, male) were divided into a control group, high-dose CPP-1 group (20 mg/mL), and low-dose CPP-1 group (10 mg/mL). We discovered that CPP-1 can exert a reparative effect on aging stress in the intestine and liver, including alleviating inflammation and oxidative damage. We revealed that CPP-1 supplementation improved the intestinal microbiota composition and repaired the intestinal barrier in the gut. Furthermore, CPP-1 was proved to modulate lipid metabolism and repair hepatocyte injury in the liver by influencing the enterohepatic axis associated with the intestinal microbiota. Therefore, we concluded that CPP-1 prevents and alleviates oxidative stress and inflammatory responses in the intestine and liver of aging mice by modulating the intestinal microbiota-related gut-liver axis to delay aging.
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Vitiligo is the most common disorder of depigmentation, which is caused by multiple factors like metabolic abnormality, oxidative stress and the disorders of immune. In recent years, several studies have used untargeted metabolomics to analyze differential metabolites in patients with vitiligo, however, the subjects in these studies were all in plain area. In our study, multivariate analysis indicated a distinct separation between the healthy subjects from plateau and plain areas in electrospray positive and negative ions modes, respectively. Similarly, a distinct separation between vitiligo patients and healthy controls from plateau and plain areas was detected in the two ions modes. Among the identified metabolites, the serum levels of sphingosine 1-phosphate (S1P) were markedly higher in vitiligo patients compare to healthy subjects in plain and markedly higher in healthy subjects in plateau compare to those in plain. There are significant differences in serum metabolome between vitiligo patients and healthy subjects in both plateau and plain areas, as well as in healthy subjects from plateau and plain areas. S1P metabolism alteration may be involved in the pathogenesis of vitiligo.
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Germinated edible seeds and sprouts have attracted consumers because of their nutritional values and health benefits. To ensure the microbial safety of the seed and sprout, emerging processing methods involving physical fields (PFs), having the characteristics of high efficiency and environmental safety, are increasingly proposed as effective decontamination processing technologies. This review summarizes recent progress on the application of PFs to germinating edible seeds, including their impact on microbial decontamination and nutritional quality and the associated influencing mechanisms in germination. The effectiveness, application scope, and limitation of the various physical techniques, including ultrasound, microwave, radio frequency, infrared heating, irradiation, pulsed light, plasma, and high-pressure processing, are symmetrically reviewed. Good application potential for improving seed germination and sprout growth is also described for promoting the accumulation of bioactive compounds in sprouts, and subsequently enhancing the antioxidant capacity under favorable PFs processing conditions. Moreover, the challenges and future directions of PFs in the application to germinated edible seeds are finally proposed. This review also attempts to provide an in-depth understanding of the effects of PFs on microbial safety and changes in nutritional properties of germinating edible seeds and a theoretical reference for the future development of PFs in processing safe sprouted seeds.
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We examined the effects of different tillage practices on plough layer soil structure and organic carbon stabilization in black soil farmland with a long-term positioning platform. The wet-sieving method and infrared spectroscopy method were used to investigate the impacts of conventional tillage (CT), no-tillage (NT), sub-soiling tillage (ST), and moldboard plowing tillage (MP) on soil aggregates distribution and organic carbon characteristics in 0-40 cm soil layers. Compared to CT, both NT and ST treatments significantly increased the proportion of large macroaggregates (>2 mm) in the topsoil layer (0-20 cm)and that of small macroaggregates (0.25-2 mm) in the subsoil layer (20-40 cm) for NT, ST, and MP. NT, ST, and MP treatments resulted in higher mean weight dia-meter (MWD) and mean geometric diameter (GMD) of soil aggregates in both the topsoil and subsoil layers. NT treatment improved organic carbon contents in bulk soil and large macroaggregates in the topsoil layer, while ST and MP enhanced organic carbon contents in bulk soil and large macroaggregates in the subsoil layer. The contribution rate of small macroaggregates organic carbon content to the total was between 68.9% and 83.4%. Furthermore, the organic carbon chemical stabilization of soil body and aggregates increased in the topsoil and subsoil layers under NT treatment compared to others. The MWD had a positive correlation with the organic carbon content and chemical stability of soil body and small macroaggregates. These findings offered a theoretical basis for understanding the impacts of different tillage practices on the stability of soil aggregate and organic carbon in black soil region.
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Carbono , Solo , FazendasRESUMO
Ecosystem health of the Chishui River Basin (CRB, a crucial ecological barrier in the upper reaches of the Yangtze River) is vital for the ecological security and sustainability of the Yangtze River Basin. We used RUSLE model, SWAT model, Fragstats and geographic detectors to construct a theoretical framework of ecosystem health assessment for CRB, and examined the spatiotemporal variations and driving factors of ecosystem health in CRB under ecological restoration from 2010 to 2020. The results showed that ecosystem service in the CRB decreased and then increased during 2010-2020 and the overall trend was downward. The overall ecosystem service function was higher in the Danxia (non-karst) area than that in the karst area. The ecosystem health was generally subhealthy, with the Danxia area being mostly extremely healthy and healthy, whereas the karst area mostly subhealthy and unhealthy. There were differences in the dominant drivers of ecosystem health between karst and Danxia areas. Vegetation, precipitation, and bedrock bareness rate were the dominant drivers in the karst area, while vegetation, land use, and precipitation were the dominant factors in Danxia area. After interaction detection, the explanatory power of impact factors increased, and the dominant interaction factor combinations in different geomorphological type regions had shown great differences. Among them, precipitationâ©normalized difference vegetation index (NDVI), precipitationâ©digital elevation model (DEM) and precipitation â© bedrock bareness rate were the dominant interaction factor combinations in the karst area, and NDVIâ©precipitation, NDVIâ©land use and NDVIâ©DEM were the dominant interaction factor combinations in Danxia area. These results would provide scientific support for health maintenance and conservation of CRB ecosystem.
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Ecossistema , Rios , ChinaRESUMO
OBJECTIVE: To investigate short-term efficacy of direct laparoscopic-assisted radical gastrectomy (LAG) versus non-curative endoscopic submucosal dissection (ESD) plus additional LAG for early gastric cancer. MATERIALS AND METHODS: 286 patients were retrospectively assigned into two groups: direct LAG group (n = 255) and additional LAG (ESD plus LAG, n = 31) group. A 1:2 propensity score matching was performed to equalize relevant confounding factors between two groups for analysis. RESULTS: Ninety-three patients were successfully matched, including 62 in the direct LAG group and 31 in the additional LAG group. A significant (P = 0.013) difference existed in the drainage removal time between the additional LAG and direct LAG group (7 d vs. 6 d). Age, sex, tumor location and surgical approach were significantly (P < 0.05) associated with complications, with age ≥ 60 years (P = 0.002) and total gastrectomy (P = 0.011) as significant independent risk factors. A significant (P = 0.023) difference existed in the surgical time between the early and late groups (193.3 ± 37.6 min vs. 165.5 ± 25.1 min). CONCLUSION: Additional LAG (D1 + lymphadenectomy) after ESD may be safe and effective even though non-curative ESD may prolong the drainage removal time and increase the difficulty of surgery.
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Ressecção Endoscópica de Mucosa , Laparoscopia , Neoplasias Gástricas , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , GastrectomiaRESUMO
Although electrospinning (e-spinning) has witnessed rapid development in recent years, it has also been criticized by environmentalists due to the use of organic solvents. Therefore, aqueous e-spinning (green e-spinning) is considered a more attractive technique. However, considering the poor water resistance and mechanical properties of electrospun (e-spun) nanofibers, cross-linking is a perfect solution. In this review, we systematically discuss the cross-linking e-spinning system for the first time, including cross-linking strategies (in situ, liquid immersion, vapor, and spray cross-linking), cross-linking mechanism (physical and chemical cross-linking) of e-spun nanofibers, and the various applications (e.g., tissue engineering, drug delivery, water treatment, food packaging, and sensors) of cross-linked e-spun nanofibers. Among them, we highlight several cross-linking methods, including UV light cross-linking, electron beam cross-linking, glutaraldehyde (and other commonly used cross-linking agents) chemical cross-linking, thermal cross-linking, and enzymatic cross-linking. Finally, we confirm the significance of cross-linking e-spinning and reveal the problems in the construction of this system.
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C-Myc overexpression contributes to multiple hallmarks of human cancer but directly targeting c-Myc is challenging. Identification of key factors involved in c-Myc dysregulation is of great significance to develop potential indirect targets for c-Myc. Herein, a collection of long non-coding RNAs (lncRNAs) interacted with c-Myc is detected in pancreatic ductal adenocarcinoma (PDAC) cells. Among them, lncRNA BCAN-AS1 is identified as the one with highest c-Myc binding enrichment. BCAN-AS1 was abnormally elevated in PDAC tumors and high BCAN-AS1 level was significantly associated with poor prognosis. Mechanistically, Smad nuclear-interacting protein 1 (SNIP1) was characterized as a new N6-methyladenosine (m6A) mediator binding to BCAN-AS1 via recognizing its m6A modification. m6A-modified BCAN-AS1 acts as a scaffold to facilitate the formation of a ternary complex together with c-Myc and SNIP1, thereby blocking S phase kinase-associated protein 2 (SKP2)-mediated c-Myc ubiquitination and degradation. Biologically, BCAN-AS1 promotes malignant phenotypes of PDAC in vitro and in vivo. Treatment of metastasis xenograft and patient-derived xenograft mouse models with in vivo-optimized antisense oligonucleotide of BCAN-AS1 effectively represses tumor growth and metastasis. These findings shed light on the pro-tumorigenic role of BCAN-AS1 and provide an innovant insight into c-Myc-interacted lncRNA in PDAC.