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AIM: Vitamin D is an essential micronutrient for multiple physiological processes, and its deficiency remains a world-wide public health problem that cannot be ignored. Dried blood spot (DBS) is a convenient tool in large-scale epidemiological studies, but its application in evaluating vitamin D status in Chinese population is still scarce. Herein, we aimed to determine the vitamin D status in Chinese pre-school children using DBS coupled with LC-MS/MS method. METHODS: We first developed a sensitive and reliable method for the determination of 25-hydroxyvitamin D (25(OH)D) in DBS samples using an ultra-high-performance liquid chromatograph coupled with triple quadrupole mass spectrometer (UHPLC-QQQ-MS/MS). Next, we conducted a pilot study to compare the 25(OH)D concentration in DBS and serum samples. Finally, the assay method was used to evaluate vitamin D status in Chinese pre-school children. RESULTS: The present method was validated to be reliable and robust for the determination of 25(OH)D in DBS samples. Comparable consistency was observed between the 25(OH)D concentration in DBS and serum samples. A total of 3826 DBS samples collected from children aged 1-7 years were determined. The median concentration of 25(OH)D was 19.57 ng/mL (interquartile range 14.73-24.36 ng/mL), and decreased from 1 to 7 years of age. In addition, 13.51% of male children and 15.12% female children are found to be deficient in 25(OH)D. CONCLUSIONS: DBS coupled with LC-MS/MS is a feasible strategy to evaluate vitamin D status in epidemiological studies. And vitamin D deficiency remains a common health problem in Chinese pre-school children.
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Air pollutants combined with Hg, Cd, Cr, Pb, etc. in many global populated areas were studied comprehensively, while our understanding towards thallium (Tl), an extremely toxic heavy metal, remains very limited. Further, the knowledge on atmospheric emissions, distribution, and the hidden risks associated with Tl is of great scarcity. Hence, this work aims to review recent data on significant sources of ambient Tl resulting from industrial activities, including Pb/Zn/Cu/Fe sulfide ore smelting, steel-making, coal burning, and cement production that involves the use of Tl-bearing wastes. Through the examination of Tl emissions and transfer pathways in the atmosphere, it is found that Tl is present at lower than ng/m3 in aerosols and air particulates but can increase to much higher levels even at 1000 µg/m3 in atmospheric fine particulate matters near the mining and smelting industrialized zones located near populated areas. This study highlights the importance of creating a comprehensive emission inventory for Tl, particularly in developing countries where this data is currently lacking. The time has come to develop a precise national emission inventory for Tl in order to prevent and mitigate the risks associated with ambient exposure to this element. This review offers novel insights for the scientific community and policy-makers in establishing effective control and management strategies to curb hidden Tl hazards derived from industrial activities.
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Engineering enzyme-substrate binding pockets is the most efficient approach for modifying catalytic activity, but is limited if the substrate binding sites are indistinct. Here, we developed a 3D convolutional neural network for predicting protein-ligand binding sites. The network was integrated by DenseNet, UNet, and self-attention for extracting features and recovering sample size. We attempted to enlarge the dataset by data augmentation, and the model achieved success rates of 48.4%, 35.5%, and 43.6% at a precision of ≥50% and 52%, 47.6%, and 58.1%. The distance of predicted and real center is ≤4 Å, which is based on SC6K, COACH420, and BU48 validation datasets. The substrate binding sites of Klebsiella variicola acid phosphatase (KvAP) and Bacillus anthracis proline 4-hydroxylase (BaP4H) were predicted using DUnet, showing high competitive performance of 53.8% and 56% of the predicted binding sites that critically affected the catalysis of KvAP and BaP4H. Virtual saturation mutagenesis was applied based on the predicted binding sites of KvAP, and the top-ranked 10 single mutations contributed to stronger enzyme-substrate binding varied while the predicted sites were different. The advantage of DUnet for predicting key residues responsible for enzyme activity further promoted the success rate of virtual mutagenesis. This study highlighted the significance of correctly predicting key binding sites for enzyme engineering.
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Aprendizado de Máquina , Sítios de Ligação , Engenharia de Proteínas/métodos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fosfatase Ácida/química , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Especificidade por Substrato , Bacillus anthracis/genética , Bacillus anthracis/enzimologia , Klebsiella/genética , Klebsiella/enzimologia , Ligantes , Ligação Proteica , Modelos Moleculares , Redes Neurais de ComputaçãoRESUMO
Thallium (Tl) is a highly toxic metal, and its contamination in soils entails high risks to human health via food chain. It remains largely unknown of the effects of applying biochar on Tl uptake in paddy systems despite that few studies have shown that biochar exhibits great potential for decreasing Tl bioavailability in soils. Herein, we examined the mitigating effects of the application of biochar (5 and 20 g/kg pristine biochar; 5 and 20 g/kg Fe/Mn-modified biochar) on Tl uptake in paddy soil and rice plant after an entire rice growth period. The results suggested that the application of Fe/Mn-modified biochar (FMBC) considerably mitigated the accumulation of Tl in different tissues of rice plants. Specifically, total Tl content in rice plants treated with FMBC-20 decreased by over 75% compared with control experiment. In addition, the amendment of FMBC in Tl-rich paddy soils can enhance the communities of microorganisms (Actinobacteria and Proteobacteria). Further analysis of the soil microbial symbiosis network revealed that FMBC promotes the living microorganisms to play modular synergistic interactions, which is crucial for FMBC-induced Tl stabilization in soils. All these findings indicated that FMBC is an efficient and environmentally friendly Tl-immobilization alternative material and can be potentially used in the remediation of Tl-contaminated paddy soils and/or cropland.
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Carvão Vegetal , Oryza , Poluentes do Solo , Solo , Tálio , Oryza/crescimento & desenvolvimento , Carvão Vegetal/química , Solo/química , Microbiologia do SoloRESUMO
The feeding of piercing-sucking insect herbivores often elicits changes in their host plants that benefit the insect.1 In addition to thwarting a host's defense responses, these phloem-feeding insects may manipulate source-sink signaling so as to increase resources consumed.2,3 To date, the molecular mechanisms underlying herbivore-induced resource reallocation remain less investigated. Brown planthopper (BPH), an important rice pest, feeds on the phloem and oviposits into leaf sheaths. BPH herbivory increases sugar accumulations 5-fold in the phloem sap of leaf sheaths and concurrently induces the expression of two clade III SWEET genes, SWEET13 and SWEET14, in leaf tissues, but not in leaf sheaths of attacked rice plants. Mutations of both genes by genome editing attenuate resistance to BPH without alterations of known chemical and physical defense responses. Moreover, BPH-elicited sugar levels in the phloem sap were significantly reduced in sweet13/14 mutants, which is likely to attenuate BPH feeding behavior on sweet13/14 mutants. In one of the two field seasons tested, the sweet13/14 mutants showed comparable yield to wild types, and in the other season, the mutants demonstrated stronger BPH resistance. These preliminary results suggested that the mutations in these SWEET transporters could enhance BPH resistance without yield penalties. Given that sweet13/14 mutants also exhibit resistance to bacterial blight pathogen, Xanthomonas oryzae pv. oryzae, these SWEET genes could serve as excellent molecular targets for the breeding of resistant rice cultivars.
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Hemípteros , Oryza , Hemípteros/fisiologia , Hemípteros/genética , Hemípteros/microbiologia , Oryza/metabolismo , Oryza/genética , Oryza/microbiologia , Animais , Herbivoria , Floema/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Comportamento Alimentar/fisiologia , Açúcares/metabolismoRESUMO
Thallium (Tl), a highly toxic heavy metal, which may pose significant environmental threats due to extensive discharge from anthropogenic activities. It is crucial to understand geochemical behavior of Tl in soils for initiating proper measures for Tl pollution control. For this purpose, transport behavior of Tl and its dominant factors in soils collected from a typically Tl-enriched depth profile, surrounding a historical tailing dump near an independent HgTl mine area in China, were investigated by using Tl isotope compositions. Results showed that an overall enrichment of Tl (48.68-375.21 mg/kg) was accompanied with As elevation (135.00-619.00 mg/kg) in the whole depth profile, and Tl and As exhibited co-migration behavior with Fe, S, K, and Rb. Geochemical fractionation of Tl unveiled by sequential extraction further indicated that Mn-/Fe-bearing minerals and clay minerals act as main hosts of Tl in the studied soils. Thallium isotopic composition and its fractionation pattern further revealed that the major contributors to high Tl levels in the depth profile were tailing and lorandite minerals, with mean contribution rate of 51.99% and 42.47%, respectively. These findings facilitate the understanding of Tl transport behavior in highly contaminated environment, providing valuable insights for developing new technologies in mining waste treatment and historical mine reclamation.
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Accumulation of cadmium (Cd) in rice is not only harmful to the growth of plants but also poses a threat to human health. Exposure to Cd triggers unfolded protein response (UPR) within cells, a process that is still not completely understood. The study demonstrated that the lack of OsbZIP39, an essential endoplasmic reticulum (ER)-resident regulator of the UPR, resulted in decreased Cd intake and reduced Cd levels in the roots, stems, and grains of rice. Upon exposure to Cd stress, GFP-OsbZIP39 translocated from ER to nucleus, initiating UPR. Further investigation revealed that Cd treatment caused changes in sphingolipid levels in the membrane, influencing the localization and activation of OsbZIP39. Yeast one-hybrid and dual-LUC assays were conducted to validate the interaction between activated OsbZIP39 and the promoter of the defensin-like gene OsCAL2, resulting in an increase in its expression. Different variations were identified in the coding region of OsbZIP39, which may explain the varying levels of Cd accumulation observed in the indica and japonica subspecies. Under Cd treatment, OsbZIP39ind exhibited a more significant enhancement in the transcription of OsCAL2 compared to OsbZIP39jap. Our data suggest that OsbZIP39 positively regulates Cd uptake in rice, offering an encouraging objective for the cultivation of low-Cd rice.
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Cádmio , Estresse do Retículo Endoplasmático , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Oryza/metabolismo , Oryza/genética , Oryza/efeitos dos fármacos , Cádmio/toxicidade , Cádmio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Defensinas/genética , Defensinas/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacosRESUMO
The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.
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Neoplasias Colorretais , Lipidômica , Fosfatidiletanolaminas , Espectrometria de Massas em Tandem , Língua , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Lipidômica/métodos , Masculino , Feminino , Língua/microbiologia , Língua/metabolismo , Língua/patologia , Língua/química , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Fosfatidiletanolaminas/metabolismo , Fosfatidiletanolaminas/análise , Idoso , Cromatografia Líquida , Lipídeos/análise , Lipídeos/química , Triglicerídeos/metabolismo , Triglicerídeos/análise , Adenoma/metabolismo , Adenoma/microbiologia , Esfingomielinas/análise , Esfingomielinas/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/química , Plasmalogênios/análise , Plasmalogênios/metabolismo , Plasmalogênios/química , Estudos de Casos e Controles , Etanolaminas/metabolismo , Etanolaminas/análise , Etanolaminas/química , Ceramidas/metabolismo , Ceramidas/análise , AdultoRESUMO
Atherosclerosis is the main pathological basis of cardiovascular diseases (CVDs). Fufang Danshen Tablet (FDT) is a traditional Chinese medicine that has been clinically used to treat CVDs for more than 40 years. Nevertheless, owing to the complexity of the ingredients, the pharmacological mechanism of FDT in the treatment of CVDs has not been fully elucidated. In this study, an integrated strategy of UFLC-Q-TOF-MS/MS, network pharmacology, molecular biology, and transcriptomics was used to elucidate the mechanisms of action of FDT in the treatment of atherosclerosis. In total, 22 absorbed constituents were identified in rat serum after oral administration of FDT. In silico, network pharmacology studies have shown that FDT regulates four key biological functional modules for the treatment of atherosclerosis: oxidative stress, cell apoptosis, energy metabolism, and immune/inflammation. In animal experiments, FDT exerted protective effects against atherosclerosis by reducing the plaque area and lipid levels in ApoE-/- mice. Furthermore, we found that FDT inhibited inflammatory macrophage accumulation by regulating the expression of Selp and Ccl2, which are both involved in monocyte adhesion and migration. The inhibition of monocyte recruitment by FDT is a new perspective to elucidate the anti-atherosclerotic mechanism of FDT, which has not been adopted in previous studies on FDT. Our results may help to elucidate the therapeutic mechanism of FDT against CVDs and provide potential therapeutic targets.
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Transcription factors (TFs) are proteins essential for regulating genetic transcriptions by binding to transcription factor binding sites (TFBSs) in DNA sequences. Accurate predictions of TFBSs can contribute to the design and construction of metabolic regulatory systems based on TFs. Although various deep-learning algorithms have been developed for predicting TFBSs, the prediction performance needs to be improved. This paper proposes a bidirectional encoder representations from transformers (BERT)-based model, called BERT-TFBS, to predict TFBSs solely based on DNA sequences. The model consists of a pre-trained BERT module (DNABERT-2), a convolutional neural network (CNN) module, a convolutional block attention module (CBAM) and an output module. The BERT-TFBS model utilizes the pre-trained DNABERT-2 module to acquire the complex long-term dependencies in DNA sequences through a transfer learning approach, and applies the CNN module and the CBAM to extract high-order local features. The proposed model is trained and tested based on 165 ENCODE ChIP-seq datasets. We conducted experiments with model variants, cross-cell-line validations and comparisons with other models. The experimental results demonstrate the effectiveness and generalization capability of BERT-TFBS in predicting TFBSs, and they show that the proposed model outperforms other deep-learning models. The source code for BERT-TFBS is available at https://github.com/ZX1998-12/BERT-TFBS.
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Redes Neurais de Computação , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Sítios de Ligação , Algoritmos , Biologia Computacional/métodos , Humanos , Aprendizado Profundo , Ligação ProteicaRESUMO
Due to inherent differences in cellular composition and metabolic behavior with host cells, tumor-harbored bacteria can discriminatorily affect tumor immune landscape. However, the mechanisms by which intracellular bacteria affect antigen presentation process between tumor cells and antigen-presenting cells (APCs) are largely unknown. The invasion behavior of attenuated Salmonella VNP20009 (VNP) into tumor cells is investigated and an attempt is made to modulate this behavior by modifying positively charged polymers on the surface of VNP. It is found that non-toxic chitosan oligosaccharide (COS) modified VNP (VNP@COS) bolsters the formation of gap junction between tumor cells and APCs by enhancing the ability of VNP to infect tumor cells. On this basis, a bacterial biohybrid is designed to promote in situ antigen cross-presentation through intracellular bacteria induced gap junction. This bacterial biohybrid also enhances the expression of major histocompatibility complex class I molecules on the surface of tumor cells through the incorporation of Mdivi-1 coupled with VNP@COS. This strategic integration serves to heighten the immunogenic exposure of tumor antigens; while, preserving the cytotoxic potency of T cells. A strategy is proposed to precisely controlling the function and local effects of microorganisms within tumors.
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Apresentação de Antígeno , Quitosana , Junções Comunicantes , Salmonella , Humanos , Quitosana/química , Linhagem Celular Tumoral , Junções Comunicantes/metabolismo , Salmonella/imunologia , Animais , Apresentação Cruzada , Camundongos , Oligossacarídeos/química , Neoplasias/imunologia , Neoplasias/patologia , Células Apresentadoras de Antígenos/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologiaRESUMO
Background: Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC). Methods: Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model. Results: We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants. Conclusion: These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.
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The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.
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Chlorella , Microalgas , Neoplasias , Animais , Camundongos , Hidrogéis , Glucose Oxidase , Fotossíntese , Hipóxia , Oxigênio , Imunoterapia , Alginatos , Microambiente TumoralRESUMO
BACKGROUND: Curcumin is a kind of natural hydrophobic polyphenol isolated from the stem of the Curcuma plant. To investigate regulatory curcumin effect on atherosclerotic endothelial cell injury. METHODS: 30 male ApoE-/- mice were selected and divided into the control group, model group, and curcumin group (n = 10). The curcumin group was treated with curcumin by gavage. Body weight, atherosclerotic plaque area, plaque cap thickness, blood lipid levels, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) content, nitric oxide (NO) content, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) content and circulating endothelial cell number of mice in each group were detected. Western blot detected NACHT, LRR, and receptor family pyrin domain-containing 3 (NLRP3) and Asc-type amino acid transporter protein 1 (ASC) protein level in mice. Human aortic endothelial cells (HAEC) were cultured to establish an atherosclerotic endothelial cell injury model in vivo. Cell counting kit-8 (CCK-8) detected the cell viability of each group. RESULTS: Body weight, atherosclerotic plaque area, plaque cap thickness, TC, TG, and LDL-C content of blood lipid levels of the curcumin group were obviously reduced as compared with the model group (p < 0.05), the content of NO and the number of circulating endothelial cells in curcumin group were obviously decreased (p < 0.05). The cell viability of the curcumin group was obviously higher than that of the model group (p < 0.05). The NO content of the curcumin group was lower than the model group (p < 0.05). The content of IL-1ß and TNF-α in the curcumin group was obviously lower than in the model group (p < 0.05). Compared with the model group, the expression of receptor family pyrin domain-containing 3 (NLRP3) and ASC protein in the curcumin group was decreased obviously (p < 0.05). CONCLUSION: Curcumin improves endothelial cell injury in atherosclerosis by inhibiting the expression of NLRP3 inflammatory bodies.
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Aterosclerose , Curcumina , Placa Aterosclerótica , Camundongos , Humanos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Curcumina/metabolismo , Placa Aterosclerótica/metabolismo , Células Endoteliais , Fator de Necrose Tumoral alfa , LDL-Colesterol/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Lipídeos , Peso Corporal , Inflamassomos/metabolismoRESUMO
Background: High-quality cardiopulmonary resuscitation (CPR) is a key element in the rescue of cardiac arrest patients but is difficult to achieve in circumstances involving aerosol transmission, such as the COVID-19 pandemic. Methods: This prospective randomized crossover trial included 30 experienced health care providers to evaluate the impact of personal protective equipment (PPE) on CPR quality and rescuer safety. Participants were asked to perform continuous CPR for 5 minutes on a manikin with three types of PPE: level D-PPE, level C-PPE, and PAPR. The primary outcome was effective chest compression per minute. Secondary outcomes were the fit factor by PortaCount, vital signs and fatigue scores before and after CPR, and perceptions related to wearing PPE. Repeated-measures ANOVA was used, and a two-tailed test value of 0.05 was considered statistically significant. Results: The rates of effective chest compressions for 5 minutes with level D-PPE, level C-PPE, and PAPRs were 82.0 ± 0.2%, 78.4 ± 0.2%, and 78.0 ± 0.2%, respectively (p = 0.584). The fit-factor test values of level C-PPE and PAPRs were 182.9 ± 39.9 vs. 198.9 ± 9.2 (p < 0.001). The differences in vital signs before and after CPR were not significantly different among the groups. In addition, the fatigue and total perception scores of wearing PPE were significantly higher for level C-PPE than PAPRs: 3.8 ± 1.6 vs. 3.0 ± 1.6 (p < 0.001) and 27.9 ± 5.4 vs. 26.0 ± 5.3 (p < 0.001), respectively. Conclusion: PAPRs are recommended when performing CPR in situations where aerosol transmission is suspected. When PAPRs are in short supply, individual fit-tested N95 masks are an alternative. This trial is registered with NCT04802109.
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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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Terapia por Acupuntura , Humanos , Reprodutibilidade dos Testes , Psicometria/métodos , Inquéritos e Questionários , Análise FatorialRESUMO
OBJECTIVES: Human heart-type fatty acid binding protein (HFABP) is a biomarker for diagnosis, risk assessment, and prognosis of acute myocardial infarction, and we aimed to establish an immunoassay for HFABP quantitation. METHODS: Human HFABP monoclonal antibodies (mAbs) were developed, evaluated by enzyme-linked immunosorbent assay, and a chemiluminescence enzyme immunoassay (CLEIA) generated. Analytical performance of the CLEIA was evaluated by measuring serum HFABP. RESULTS: The prokaryotically expressed rHFABP was purified and four anti-HFABP mAbs with superior detection performance were obtained after immunizing BALB/c mice. MAbs 2B8 and 6B3 were selected as respective capture and detection antibodies for HFABP measurement by CLEIA (detection range, 0.01-128 µg/L). Results using the CLEIA showed excellent correlation (r, 0.9622) and the correlation coefficient was 0.9809 (P < 0.05) by the Tukey test statistical analysis with those of latex-enhanced immunoturbidimetry in hospitals. CONCLUSION: Our mAbs and CLEIA for HFABP detection represent new diagnostic tools for measurement of human serum HFABP.
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Anticorpos Monoclonais , Luminescência , Animais , Camundongos , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , Imunoensaio/métodos , BiomarcadoresRESUMO
In this work, by comparing and analyzing dynamic biasing InGaAs/InAlAs avalanche photodiodes(APDs) with different active areas, it is found that they have different noise suppression frequency ranges. The upper limit frequency(defined as the frequency at which the noise suppression effect begins to fail) of InGaAs/InAlAs APDs with active area diameter of 50â µm, 100â µm and 200â µm are 2400â MHz, 1990MHz and 1400â MHz respectively. In addition, for InGaAs/InAlAs APDs with an active area diameter of 50â µm, 100â µm and 200â µm, their optimal frequencies of dynamic biasing (defined as the frequency corresponding to the optimal SNR) are 1877MHz, 1670â MHz and 1075â MHz respectively. At last, applying dynamic biasing technology, it achieves a useful gain of 6698.1, which is much greater than that of DC bias (47.2), and this technology has the potential to be applied in high sensitivity laser radar receivers.
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As antimony (Sb) has been increasingly used in manufacturing industries (e.g., alloy, polymer and electronics industries), Sb contamination in the soil environment becomes widely reported and has drawn growing attention due to the toxicity of Sb to living organisms. Whether soil-dwelling organisms can tolerate Sb toxicity and maintain their ecological functions remains poorly understood. Using a cosmopolitan, ecologically important earthworm species (Eisenia fetida) as an ideal model organism, we examine the effects of Sb on the physiological, molecular and behavioural responses of earthworms to different levels of Sb contamination in soil (0, 10, 50, 100, 250 and 500 mg/kg). We found that earthworms could tolerate heavy Sb contamination (100 mg/kg) by boosting their antioxidant defence (POD and GST) and immune systems (ACP) so that their body weight and survival rate were sustained (c.f. control). However, these systems were compromised under extreme Sb contamination (500 mg/kg), leading to mortality. As such, earthworms exhibited avoidance behaviour to escape from the Sb-contaminated soil, implying the loss of their ecological contributions to the environment (e.g., increase in soil aeration and maintenance of soil structure). By measuring various types of biomarkers along a concentration gradient, this study provides a mechanistic understanding of how earthworms resist or succumb to Sb toxicity. Since extreme Sb contamination in soil (>100 mg/kg) is rarely found in nature, we are optimistic that the health and performance of earthworms are not influenced by Sb in most circumstances, but regular monitoring of Sb in soil is recommended to ensure the integrity and functioning of soil environment. Further studies are recommended to evaluate the long-term impact of Sb in the soil ecosystem through bioaccumulation and trophic transfer among soil-dwelling organisms.
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Oligoquetos , Poluentes do Solo , Animais , Solo/química , Oligoquetos/fisiologia , Antimônio/toxicidade , Antimônio/análise , Ecossistema , Poluentes do Solo/toxicidade , Poluentes do Solo/análiseRESUMO
Glioblastomas (GBMs) are aggressive primary brain tumors with fatal outcome. Traditional chemo-radiotherapy has poor therapeutic effect and significant side effects, due to the drug and radiotherapy (RT) resistance, natural blood-brain barrier, and high-dose RT damage. Even more, tumor-associated monocytes (macrophages and microglia, TAMs) constitute up to 30%-50% of the GBM cellular content, and the tumor microenvironment (TME) in GBM is extremely immunosuppressive. Here, we synthesized nanoparticles (D@MLL) that hitchhike on circulating monocytes to target intracranial GBMs with the assistance of low-dose RT. The chemical construction of D@MLL was DOX·HCl loaded MMP-2 peptide-liposome, which could target monocytes by the surface modified lipoteichoic acid. First, low-dose RT at the tumor site increases monocyte chemotaxis and induces M1 type polarization of TAMs. Subsequently, the intravenous injected D@MLL targets circulating monocytes and hitchhikes with them to the central site of the GBM area. DOX·HCl was then released by the MMP-2 response, inducing immunogenic cell death, releasing calreticulin and high-mobility group box 1. This further contributed to TAMs M1-type polarization, dendritic cell maturation, and T cell activation. This study demonstrates the therapeutic advantages of D@MLL delivered by endogenous monocytes to GBM sites after low-dose RT, and it provides a high-precision treatment for GBMs.