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ETHNOPHARMACOLOGICAL RELEVANCE: Celastrus orbiculatus Thunb. is an ancient traditional Chinese herb with a long history of medicinal use. The ethyl acetate extract of Celastrus orbiculatus Thunb. (COE) has been shown to have anti-tumor effects in various preclinical studies. However, the anti-invasive and metastatic efficacy of COE in non-small cell lung cancer (NSCLC) and the mechanism by which COE regulates cellular oxidation levels are yet to be elucidated. AIM: To study the anti-dissemination effect of COE on NSCLC and to elucidate the molecular mechanism of COE in regulating cellular oxidation levels and its effect on lung cancer invasion and metastasis. METHODS: CCK-8 assay was used to detect the toxic effects of COE on NSCLC. Transwell assay and high-content imaging was used to detect the Motility of NSCLC. Transmission electron microscopy and three-dimensional (3D) imaging of mitochondrial fluorescence were employed to detect the number and structure of mitochondria. JC-1 probe was used to detect the level of mitochondrial membrane potential. Firefly luciferase assay was used to detect the level of total intracellular ATP. MitoSox probe and DCFH-DA probe were applied to detect the level of reactive oxygen species (ROS) inside the mitochondria and the total intracellular ROS, respectively. Immunohistochemistry was used to detect protein expression in xenograft tumors. RESULTS: COE inhibited motility and induced DJ-1 downregulation in NSCLC at low toxic concentrations, and the antiseptic effect of COE was reduced significantly after the overexpression of DJ-1. COE induced structural disruption of mitochondria in NSCLC and accumulation of superoxide compounds, decreased the volume of membrane potential depolarization, and impaired energy production, ultimately leading to a large accumulation of ROS at the cellular level. The antioxidant acetylcysteine (NAC) significantly reversed the antiseptic capacity of COE. In a xenograft tumor model, protein expression of DJ-1, E-cadherin, N-cadherin, and MMP-2 in COE group was significantly changed compared to the model group. CONCLUSION: In the present study, COE inhibited NSCLC invasion and metastasis and was associated with the downregulation of DJ-1 and elevated ROS. COE-mediated downregulation of DJ-1 may be the primary cause of mitochondrial structural and functional dysfunction in NSCLC, eventually leading to ROS accumulation.
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Carcinoma Pulmonar de Células não Pequenas , Celastrus , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Celastrus/química , Espécies Reativas de Oxigênio , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Linhagem Celular Tumoral , Neoplasias Pulmonares/tratamento farmacológico , MitocôndriasRESUMO
Developing efficient strategies for specific detection of cysteine (Cys) is of great importance for identifying complicated biological roles in physiological and pathological processes. Herein, an ultrasensitive red-emission fluorescent probe (termed 1) is constructed for specific detection and biological visualization of Cys. The linked-anthocyanin fluorophore modified with a twisted N, N-diethylamino moiety shows improved red-shifted emission (642 nm) and absolute quantum yield (0.224 in dimethyl sulfoxide), as well as minimal fluorescence background signal and good water solubility. Meanwhile, utilizing acryloyl chloride as recognition group endows the probe 1 with excellent sensitivity and selectivity towards Cys (limit of detection: 2.93 nM). More importantly, the in vitro and in vivo results confirm that the probe 1 has the capacity of fluorescence imaging of Cys and good biological safety, which holds great promise for bioanalysis and biosensing of Cys.
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Direct measurements of gaseous elemental mercury (GEM) exchanges over global ecosystems are challenging and require extensive and costly measurement systems. Here, we explore the use of atmospheric GEM concentration variability and passive samplers to assess underlying ecosystem GEM exchanges at two rural temperate forests in the northeastern United States. We find strong temporal alignments between atmospheric GEM concentration declines and ecosystem GEM deposition in spring at both forests, which followed patterns of CO2 and suggests that ambient air GEM concentration monitoring provides a proxy measurement to assess forest GEM sinks. In fall, we observe GEM concentration increases and reversal of GEM fluxes to emissions, but with poor temporal alignments. Diel GEM concentration variability did not correspond to diel patterns of ecosystem GEM fluxes, which is driven by boundary layer dynamics with different atmospheric mixing depths during day- and nighttime. Passive samplers (PASs) deployed to measure vertical GEM gradients across six heights throughout one of the forest canopies showed excellent agreements with active measurements in detecting seasonal concentration patterns at all deployment heights. We find frequent qualitative agreement between the direction of active and PAS derived concentration gradients, but small concentration differences over small (1.3 and 4.9 m) distances prevent a quantitative comparison of methods. Furthermore, time-averaged GEM concentration gradient measurements are always biased towards stable nighttime periods, while ecosystem GEM fluxes are dominated by daytime exchanges, which results in the inability of integrated measurements such as PAS to correctly quantify forest GEM exchanges. We conclude that concentration measurements both via active and passive sampling can serve as proxies to assess underlying ecosystem GEM sinks and sources, but that the use of passive samplers to quantify GEM exchange via gradient measurements is limited due their strong nighttime biases.
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Mercúrio , Ecossistema , Gases , Florestas , AtmosferaRESUMO
OBJECTIVE: We sought to investigate the reasons why spondyloarthritis (SpA) patients failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) and the influences of different initial cDMARDs on the likelihood of a switch to biologics. METHODS: SpA patients were divided into a conventional drug maintenance group and a biologics conversion group to determine the causes of conversion to biologics. Then, we divided all patients into three groups according to different initial cDMARDs, NSAID monotherapy, NSAID + (sulfasalazine or thalidomide) double combination, and NSAID + sulfasalazine + thalidomide triple combination therapy groups, to clarify the influence of initial treatment on later conversion to biologics. RESULTS: This study includes 202 patients, including 97 patients in the conventional drug maintenance group and 105 patients in the biologics conversion group. The mean age of the conventional drug maintenance group was higher than that of the biologics conversion group (40.8 ± 14.3 vs. 33.8 ± 12.3 years, P < 0.05). Uveitis (OR 5.356, P < 0.05) is positively correlated with conversion to biological therapy, while age (OR 0.940, P < 0.05) is negatively correlated. The proportion of NSAID monotherapy, double combination, and triple combination groups converted to biological agents was 80%, 51.1%, and 23.2%, respectively (P < 0.05). CONCLUSION: Age and uveitis are related to conversion to biologics therapy. The early combination of sulfasalazine and thalidomide with NSAIDs may lower the probability of conversion to biologics therapy in the later stage and offer a new option for patients with limited use of biologics in SpA patients. Key Points ⢠Patients' move to biologics may be caused mostly by inadequate disease control by conventional oral medications. ⢠Regardless of axial vs. peripheral joint involvement, combination drug therapy was superior to single drug therapy in controlling SpA and decreasing the probability of conversion to a biological agent. ⢠For SpA patients who are not candidates for biologics due to contraindications or other reasons, early combination application of NSAIDs, sulfasalazine, and thalidomide may be a new choice.
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AbstractIn this study, Chlorella and Scenedesmus were inoculated in biogas slurry medium with initial inoculum (OD680) of 0.05, 0.1, 0.2, and 0.3, respectively, and 5% CO2 was continuously injected. The study aimed to examine the carbon sequestration capacity of Chlorella and Scenedesmus, as well as the effectiveness of removing pollutants such as TN, TP, and COD in biogas slurry medium. Additionally, an economic efficiency analysis of energy consumption was conducted. The group with an initial inoculum (OD680) of 0.3 for both types of microalgae exhibited better tolerance to pollutants, entered the logarithmic growth stage earlier, promoted nutrient removal, achieved higher energy efficiency, and reduced carbon emissions compared to the other groups. The highest carbon sequestration rates were 18.03% for Chlorella and 11.05% for Scenedesmus. Furthermore, Chlorella demonstrated corresponding nutrient removal efficiencies of 83.03% for TN, 99.84% for TP, and 90.06% for COD, while Scenedesmus exhibited removal efficiencies of 66.35% for TN, 98.74% for TP, and 77.71% for COD. The highest energy efficiency for pollutants and CO2 removal rates for Chlorella were 49.51 ± 2.20 and 9.91 ± 0.44 USD-1, respectively. In conclusion, the findings demonstrate the feasibility of using microalgae for simultaneous purification of biogas and biogas slurry. In this study, Chlorella and Scenedesmus were inoculated in biogas slurry medium with initial inoculum (OD680) of 0.05, 0.1, 0.2, and 0.3, respectively, and 5% CO2 was continuously injected. The study aimed to examine the carbon sequestration capacity of Chlorella and Scenedesmus, as well as the effectiveness of removing pollutants such as TN, TP, and COD in biogas slurry medium. Additionally, an economic efficiency analysis of energy consumption was conducted. The group with an initial inoculum (OD680) of 0.3 for both types of microalgae exhibited better tolerance to pollutants, entered the logarithmic growth stage earlier, promoted nutrient removal, achieved higher energy efficiency, and reduced carbon emissions compared to the other groups. The highest carbon sequestration rates were 18.03% for Chlorella and 11.05% for Scenedesmus. Furthermore, Chlorella demonstrated corresponding nutrient removal efficiencies of 83.03% for TN, 99.84% for TP, and 90.06% for COD, while Scenedesmus exhibited removal efficiencies of 66.35% for TN, 98.74% for TP, and 77.71% for COD. The highest energy efficiency for pollutants and CO2 removal rates for Chlorella were 49.51 ± 2.20 and 9.91 ± 0.44 USD-1, respectively. In conclusion, the findings demonstrate the feasibility of using microalgae for simultaneous purification of biogas and biogas slurry.
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T cells play an important role in regulating immune system balance. Sepsis-associated immunosuppression causes apoptosis of T cells and a decrease in their number. Previously, artesunate was found to have an immunomodulatory effect on immunosuppression in model mice with cecal ligation and puncture (CLP)-induced sepsis. In the present study, mouse sepsis models of CLP and CLP with secondary infection were established and treated with artesunate in order to examine the effect of artesunate on adaptive immune response in sepsis-related immunosuppression. The results showed that artesunate treatment could increase the survival rate of CLP mice with secondary Pseudomonas aeruginosa infection, increase the bacterial clearance rate, and also increase the level of the pro-inflammatory cytokine TNF-α. In addition, artesunate resulted in an increase in the number of T cells, CD4+ T cells and CD8+ T cells, and inhibited CD4+ and CD8+ T-cell apoptosis. Artesunate was also found to inhibit the expression of the inhibitory receptors of PD-1, CTLA-4, and BTLA, but it did not affect the expression of Tim-3. Additionally, artesunate significantly increased the phosphorylated ERK level of CD4+ T cells and CD8+ T cells and inhibited mitochondrial pathway-mediated apoptosis in CLP mice with Pseudomonas aeruginosa infection. These findings reveal that artesunate has an immunomodulatory effect on the adaptive immune response in sepsis. These effects include an increase in the numbers of T cells, CD4+ T cells, and CD8+ T cells through inhibition of the expression of inhibitory receptors and promotion of the MAPK/ERK pathway.
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The microsporidian Enterocytozoon hepatopenaei from Penaeus vannamei (EHPPv) was redescribed on the basis of spore morphology, life cycle, pathology, and molecular character. Compared with the Enterocytozoon hepatopenaei isolated from Penaeus monodon (EHPPm), described by Tourtip et al. in 2009, new features were found in EHPPv. Electron microscopy demonstrated that EHPPv was closely associated with the nucleus of host cell. The merogony and sporogony phages were in direct contact with the cytoplasm of host cells, whereas some of the sporoblasts and the spores were surrounded by the interfacial envelope. Mature spores of EHPPv were oval and monokaryotic, measuring 1.65 ± 0.15 µm × 0.92 ± 0.05 µm. Spores possessed many polyribosomes around a bipartite polaroplast and the polar filament with 4-5 coils in two rows. Phylogenetic analyses showed all Enterocytozoon hepatopenaei isolates shared a common ancestor. Based on the morphological and molecular analyses, we propose the establishment of a new genus Ecytonucleospora and transferring Enterocytozoon hepatopenaei to the genus Ecytonucleospora, retaining the specific epithet hepatopenaei that Tourtip et al. proposed in recognition of their first research, as the new combination Ecytonucleospora hepatopenaei n. comb. Furthermore, it was suggested Enterospora nucleophila, Enterocytozoon sp. isolate RA19015_21, and Enterocytozoon schreckii be assigned into this new genus.
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BACKGROUND: Peritonitis is the most important complication of peritoneal dialysis (PD) and coagulase-negative staphylococci (CNS) are a frequent cause of dialysis-related infections. The association between SCCmec typing with psm-mec positivity in staphylococci and PD-related infections has not been identified. We aim to investigate the molecular epidemiology of CNS isolated from PD-peritonitis in a single Chinese center, focusing on the genetic determinants conferring methicillin resistance. METHODS: We collected 10 genetically unrelated CNS isolates from 10 patients with CNS PD-related peritonitis. The patients were divided into two groups based on the results of MIC to oxacillin: the methicillin-resistant CNS (MRCNS) and methicillin-sensitive CNS (MSCNS) groups. The biofilm formation group (BFG) and the non-biofilm formation group (NBFG) were used as the control groups. Phenotypic and molecular methods were used to analyze SCCmec types I, II and III, associated genes and biofilm formation and the existence of psm-mec. The demographic data and clinical indicators were collected. RESULTS: Ten CNS PD-related peritonitis patients were enrolled for this study. There were 6 MRCNS and 4 MRCNS isolates. SCCmec types were fully determined in 10 isolates. Seven staphylococci (70%) carried SCCmec, of which 4 isolates carried single SCCmec type I (40%) and 3 isolates had multiple SCCmec elements (I + III). Of the 6 MRCNS isolates, 3 carried SCCmec type I (50%) and 2 isolates carried SCCmec type I + III (33.3%). A high diversity of ccr types, mec complexes and ccr-mec complex combinations was identified among the 10 CNS isolates. The psm-mec gene was detected in 2/10 (20%) CNS isolates. There was no mutation in the psm-mec gene. CONCLUSIONS: The majority of isolates were hospital-associated isolates. Furthermore, 2 psm-mec positive isolates were MRCNS in the NBFG. The PD patients frequent exposure to hospital would be the main risk factor. The presence of the psm-mec signal in the spectra of the MRCNS tested here demonstrates the presence of certain SCCmec cassettes that convey methicillin resistance.
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Cancer is a major public health issue globally and is one of the leading causes of death. Although available treatments improve the survival rate of some cases, many advanced tumors are insensitive to these treatments. Cancer cell differentiation reverts the malignant phenotype to its original state and may even induce differentiation into cell types found in other tissues. Leveraging differentiation-inducing therapy in high-grade tumor masses offers a less aggressive strategy to curb tumor progression and heightens chemotherapy sensitivity. Differentiation-inducing therapy has been demonstrated to be effective in a variety of tumor cells. For example, differentiation therapy has become the first choice for acute promyelocytic leukemia, with the cure rate of more than 90%. Although an appealing concept, the mechanism and clinical drugs used in differentiation therapy are still in their nascent stage, warranting further investigation. In this review, we examine the current differentiation-inducing therapeutic approach and discuss the clinical applications as well as the underlying biological basis of differentiation-inducing agents.
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Background: Previous genetic-epidemiological studies considered TERT (rs2736100), CCDC26 (rs4295627), CDKN2A/B (rs4977756) and RTEL1 (rs6010620) gene polymorphisms as the risk factors specific to glioma. However, the data samples of previous genetic-epidemiological studies are modest to determine whether they have definite association with glioma. Method: The study paid attention to systematically searching databases of PubMed, Embase, Web of Science (WoS), Scopus, Cochrane Library and Google Scholars. Meta-analysis under 5 genetic models, namely recessive model (RM), over-dominant model (O-DM), allele model (AM), co-dominant model (C-DM) and dominant model (DM) was conducted for generating odds ratios (ORs) and 95% confidence intervals (CIs). That was accompanied by subgroup analyses according to various racial groups. The software STATA 17.0 MP was implemented in the study. Result: 21 articles were collected. According to data analysis results, in four genetic models (AM, RM, DM and C-DM) TERT gene rs2736100 polymorphism, CCDC26 gene rs4295627 polymorphism, CDKN2A/B gene rs4977756 polymorphism and RTEL1 gene rs6010620 polymorphisms increased the risk of glioma in Caucasians to different degrees. In Asian populations, the CCDC26 gene rs4295627 polymorphism and CDKN2A/B gene rs4977756 polymorphism did not exhibit a relevance to the risk of glioma. It is suggested to cautiously explain these results as the sample size is small. Conclusion: The current meta-analysis suggested that the SNP of TERT (rs2736100), CCDC26 (rs4295627), CDKN2A/B (rs4977756) and RTEL1 (rs6010620) genes in glioma might increase risk of glioma, but there are ethnic differences. Further studies evaluating these polymorphisms and glioma risk are warranted.
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The recent development of two-dimensional magnetic and sliding-ferroelectric van der Waals (vdW) materials opens a new way to realize vdW sliding multiferroic tunnel junctions (MFTJs) for low-power nonvolatile memory applications. Here, we propose and investigate full electrical control of four nonvolatile resistance states in sliding MFTJs, Au/CrI3/bilayer h-BN/CrI3-MnBi2Te4/Au, via first principles. We found four stable states associated with different polarization orientations in bilayer h-BN and magnetization alignment in two CrI3 magnetic layers, which can be controlled purely by electrical voltage and current, respectively. The MFTJ has a giant tunneling magnetoresistance (TMR) of â¼10 000% (2000% in the presence of SOC) and a sizeable tunneling electroresistance (TER) of â¼70%. The write performance is explored by spin-transfer-torque calculations which show an impressive low critical current (â¼1.5 × 1010 A m-2) to switch the magnetization of the free layer of CrI3, while antiferromagnetic MnBi2Te4 pins the reference layer with a large interfacial exchange coupling.
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In order to expand the application of PLLA in the packaging field, improving its toughness and antibacterial activity has been widely concerned. However, seldom researches can simultaneously efficiently improve the toughness and antibacterial activity of PLLA by adding one kind of additions. To address above problems, the bifunctional branched poly(butylene adipate) ionomer additive (b-PBAUi) was synthesized. For b-PBAUi, its branched structure not only increased the plasticizing effect of additive, but also acted as reaction sites to introduce more antibacterial ionic salt. Due to the special structure of b-PBAUi, PLLA/b-PBAUi blends achieved excellent toughness and antibacterial efficiency. The elongation of blend reached 125 % even by adding 5 wt% b-PBAUi, which was 10 times higher than that of PLLA. From the analysis of phase morphology, it could be found that the microvoids promoting tensile yielding was the main tensile toughening mechanism for PLLA/b-PBAUi blends. In addition, the antibacterial activity of PLLA was significantly improved by adding b-PBAUi. For PLLA/b-PBAUi10 and PLLA/b-PBAUi15, the antibacterial efficiency against E. coli and S. aureus bacteria exceeded 99.0 %. By comprehensive consideration, the optimal blend ratio was achieved by PLLA/b-PBAUi10 due to its excellent toughness and antibacterial efficiency.
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Mercury is a heavy metal with extreme toxicity. Thus, it is of significance to develop an effective method for mercury ion detection with high performance. In this study, carbon dots doped with nitrogen and silicon (N,Si/CQDs) were successfully prepared from folic acid and N-[3-(trimethoxysily)propyl]-ethylenediamine. The N,Si/CQDs show an obvious cyan fluorescence of 460 nm with the radiation of 350 nm. The existence of mercury ions induces the fluorescence quenching of N,Si/CQDs due to photoinduced electron transfer, which was applied for the sensitive sensing of Hg(II). More importantly, the practical application of the N,Si/CQD probe was confirmed by measurements of Hg(II) in real samples of lake water, sorghum and rice. In addition, the N,Si/CQD nanoprobe was integrated on a sensing strip for specific detection of Hg(II). Quantitative measurement of Hg(II) was realized by the outstanding linearity between the diameter (or fluorescence intensity) of the fluorescence quenching ring and the concentration of mercury ions. The sensor shows potential for rapid detection with a triple signal readout on-site and represents a larger step towards practical applications.
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OBJECTIVES: Mapping computed tomography (CT) number to material property dominates the proton range uncertainty. This work aims to develop a physics-constrained deep learning-based multimodal imaging (PDMI) framework to integrate physics, deep learning, magnetic resonance imaging (MRI), and advanced dual-energy CT (DECT) to derive accurate patient mass density maps. METHODS: Seven tissue substitute MRI phantoms were used for validation including adipose, brain, muscle, liver, skin, spongiosa, 45% hydroxyapatite (HA) bone. MRI images were acquired using T1-weighted Dixon and T2-weighted short tau inversion recovery sequences. Training inputs are from MRI and twin-beam dual-energy images acquired at 120kVp with gold/tin filters. The feasibility investigation included an empirical model and four residual networks (ResNet) derived from different training inputs and strategies by PDMI framework. PRN-MR-DE and RN-MR-DE denote ResNet (RN) trained with and without a physics constraint (P) using MRI (MR) and DECT (DE) images. PRN-DE stands for RN trained with a physics constraint using only DE images. A retrospective study using institutional patient data was also conducted to investigate the feasibility of the proposed framework. RESULTS: For the tissue surrogate study, PRN-MR-DE, PRN-DE, and RN-MR-DE result in mean mass density errors: -0.72%/2.62%/-3.58% for adipose; -0.03%/-0.61%/-0.18% for muscle; -0.58%/-1.36%/-4.86% for 45% HA bone. The retrospective patient study indicated that PRN-MR-DE predicted the densities of soft tissue and bone within expected intervals based on the literature survey, while PRN-DE generated large density deviations. CONCLUSIONS: The proposed PDMI framework can generate accurate mass density maps using MRI and DECT images. The supervised learning can further enhance model efficacy, making PRN-MR-DE outperform RN-MR-DE. The patient investigation also shows that the framework can potentially improve proton range uncertainty with accurate patient mass density maps. ADVANCES IN KNOWLEDGE: PDMI framework is proposed for the first time to inform DL models by physics insights and leverage the information from MRI to derive accurate mass density maps.
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PURPOSE: This study aims to develop and validate a concise tool for evaluating acupuncture expectancy that is easy to understand and conforms to acupuncture characteristics. MATERIALS AND METHODS: A draft was created using the Delphi consensus method. Reliability, validity, discrimination, and feasibility tests were conducted at the item and scale levels. RESULTS: The scale themes were defined as disease-related, treatment-related, process-related, and outcome-related. After two rounds of Delphi surveys with good experts' reliability (authority coefficients of experts were 0.86 and 0.87 in the two rounds) and agreement (Kendall's concordance coefficient of the participants were 0.33 and 0.15 in the two rounds, P < 0.05), 11 items (the mean score for item importance, full mark ratios, and coefficient of variation of items were ≥3.5, ≥25%, and ≤0.30, respectively) were included in the draft. A total of 145 individuals were recruited to test the draft. Reliability was assessed by Cronbach's α coefficient (0.90), split-half reliability coefficient (0.89), and test-retest reliability (Pearson's coefficient = 0.74, P < 0.05). Content validity was assessed by the content validity index (Item-CVI ≥ 0.78 and Scale-CVI/Ave = 0.92), and a confirmatory factor analysis was performed to assess the construct validity. The discrimination of scale items was evaluated by the critical ratio (CR > 3.00) and the homogeneity test (item-total correlations >0.40). Feasibility was assessed through the acceptance rate (recovery rate = 98.60%, response rate = 100%), completion rate (100%), and completion time (4.99 ± 6.80 min). CONCLUSION: The patients' expectancy scale of acupuncture (PESA) consists of 11 items with four themes, disease-related, treatment-related, process-related, and outcome-related. It has great reliability, validity, discrimination, and feasibility and has the potential to evaluate acupuncture expectancy in clinical trials.
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Violet phosphorene (vP), a two-dimensional structure with various unique properties, has attracted much attention recently. The electromechanical behaviour, a mechanical-electrical-thermal coupling failure behaviour, of supported and suspended vP nanoflakes has been investigated by the c-AFM nanoindentation method under different loads and bias voltages in this work. A bump due to the oxidation caused by electric current-induced local heating was observed for the supported vP on substrates under mild load and bias voltage. A concave morphology was observed when a load of 1500 nN and a bias voltage of 10 V were applied. No bump was observed for the suspended vP due to the larger contact area between the probe and the sample, resulting in a lower temperature. Fatigue damage was observed for the vP nanoflakes under constant load and a cycled bias voltage from 10 V to -10 V. The electromechanical behaviour of vP was also analyzed through its specific heat capacity and conductivity by density functional theory.
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Clinical evidence has indicated that tumor-colonizing bacteria would be closely related to the tumor development and therapeutic responses. Selectively eliminating bacteria within tumors may be an attractive approach to enhance cancer treatment without additional side effects. Herein, we found that owing to the high affinity between the membrane protein Fap-2 on Fusobacterium nucleatum (F. nucleatum) and D-galactose-ß (1-3)-N-acetyl-D-galactosamine (Gal-GalNAc) overexpressed on colorectal tumor cells, F. nucleatum would colonize in colorectal tumors, as evidenced by both clinical samples and animal tumor models. Notably, F. nucleatum colonized in colorectal tumors would lead to immunosuppressive tumor microenvironment, greatly reducing their responses to immune checkpoint blockade (ICB) therapy. Inspired by this finding, we designed a F. nucleatum-mimetic nanomedicine by fusing F. nucleatum cytoplasmic membrane (FM) with Colistin loaded liposomes to achieve selectively killing tumor-colonizing F. nucleatum without affecting gut microbes. As the results, the therapeutic responses of F. nucleatum-colonized tumors to ICB therapies could be successfully restored, as demonstrated in F. nucleatum-infected subcutaneous CT-26 tumor model, chemical-induced spontaneous colorectal cancer models and MC-38 tumor model. In summary, our work presented a F. nucleatum-Mimicking nanomedicine which could selectively eliminate tumor-colonized bacteria, promising for enhancing the responses of cancer immunotherapy against F. nucleatum-colonized colorectal cancer. This article is protected by copyright. All rights reserved.
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Objective: The objective of this study is to systematically evaluate prediction models for post-thrombectomy brain edema in acute ischemic stroke (AIS) patients. This analysis aims to equip clinicians with evidence-based guidance for the selection of appropriate prediction models, thereby facilitating the early identification of patients at risk of developing brain edema post-surgery. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, and Vip, aiming to identify studies on prediction models for post-thrombectomy brain edema in AIS patients up to January 2023. Reference lists of relevant articles were also inspected. Two reviewers independently screened the literature and extracted data. The Prediction Model Risk of Bias Assessment Tool (PROBAST) and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines were employed to assess study bias and literature quality, respectively. We then used random-effects bivariate meta-analysis models to summarize the studies. Results: The review included five articles, yielding 10 models. These models exhibited a relatively high risk of bias. Random effects model demonstrated that the AUC was 0.858 (95% CI 0.817-0.899). Conclusion: Despite the promising discriminative ability shown by studies on prediction models for post-thrombectomy brain edema in AIS patients, concerns related to a high risk of bias and limited external validation remain. Future research should prioritize the external validation and optimization of these models. There is an urgent need for large-scale, multicenter studies to develop robust, user-friendly models for real-world clinical application. Systematic review registration: https://www.crd.york.ac.uk, unique Identifier: CRD42022382790.