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Importance: Access to timely dermatologic care remains a challenge, especially for patients with new skin lesions. Assessing the efficiency of new triage pathways may assist in better resource allocation and shorter time to care. Objective: To evaluate whether a rule-based triage system was associated with better skin cancer risk stratification of patients and reduced wait times. Design, Setting, and Participants: This retrospective quality improvement cohort study of patients referred to Stanford University dermatology clinics was conducted between November 2017 and January 2023. A rules-based triage system based on a priori-determined high-risk lesion characteristics was implemented. Exposures: Referral reasons and risk factors of patients provided by their primary care physicians. Main Outcomes and Measures: Biopsy results of patients (diagnosis of any skin cancer and melanoma) at their visit or within 6 months after the visit. Regression models were used to assess the association between risk factors at referral and (1) biopsy outcomes and (2) time to first visit, adjusting for sociodemographic factors. Results: Among 37â¯478 patients (mean [SD] age, 54 (18) years; 21â¯292 women [57%]), the rates of aggregate biopsy, malignant biopsy specimens, and melanoma were comparable across patients seen after (n = 12â¯302) and before (n = 25â¯176) the implementation of the new triage pathway. Patients seen through the lesion pathway had a higher risk of having malignant biopsy results (adjusted risk ratio [aRR], 1.6; 95% CI, 1.4-1.9) and melanoma (aRR, 2.0; 95% CI, 1.2-3.2) than those not seen through the pathway. Lesions that were concerning to referring clinicians for skin cancer were associated with an increased risk of skin cancer (all skin cancer: aRR, 2.8; 95% CI, 2.2-3.5; melanoma: aRR, 2.02; 95% CI, 1.1-3.7). Patients in the 3 high-risk lesion groups were seen faster in the new triage pathway (mean reduction, 26 days; 95% CI, 18-34 days). Conclusions and Relevance: In this study, a new automated, rules-based referral pathway was implemented that expedited care for patients with high-risk skin cancer. This reform may have contributed to improving patient stratification, reducing the time from referral to first encounter, and maintaining accuracy in identifying malignant lesions. The findings highlight the potential to optimize clinical resource allocation by better risk stratification of referred patients.
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Melanoma , Encaminhamento e Consulta , Neoplasias Cutâneas , Triagem , Humanos , Triagem/métodos , Feminino , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Medição de Risco/métodos , Melanoma/diagnóstico , Melanoma/patologia , Adulto , Idoso , Biópsia , Fatores de Risco , Melhoria de Qualidade , Tempo para o TratamentoRESUMO
Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions.
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Microfluídica , Trombose , Humanos , Células Endoteliais , Linhagem Celular , Trombose/patologia , Estresse MecânicoRESUMO
The aim of this experiment is to evaluate the effects of adding porous zinc oxide, plant polyphenols, and their combination to diets without antibiotics and high-dose zinc oxide on the growth performance, diarrhea incidence, intestinal morphology, and microbial diversity of weaned piglets. A total of 150 Duroc × Landrace × Large White weaned piglets were allocated to one of five diets in a randomized complete block design with six replicates and five piglets per replicate. The experimental period was 42 d, divided into two feeding stages: pre-starter (0-14 d) and starter (14-42 d). In the pre-starter stage, the negative control group (NC) was fed a basal diet, the positive control group (PC) was fed a basal diet with 2000 mg/kg of zinc oxide, the porous zinc oxide group (PZ) was fed a basal diet with 500 mg/kg of porous zinc oxide, the plant polyphenol group (PP) was fed a basal diet with 1500 mg/kg of plant polyphenols, and the combination group (PZ + PP) was fed a basal diet with 500 mg/kg of porous zinc oxide and 1500 mg/kg of plant polyphenols. In the starter stage, the NC, PC, and PZ groups were fed a basal diet, while the PP and PZ + PP groups were fed a basal diet with 1000 mg/kg of plant polyphenols. The results showed that, (1) compared with the PZ group, adding plant polyphenols to the diet showed a trend of increasing the ADFI of weaned piglets from 14 to 28 d (p = 0.099). From days 28 to 42 and days 0 to 42, porous zinc oxide and the combination of porous zinc oxide and plant polyphenols added to the control diet improved the FCR to the level observed in pigs fed the PC diet. (2) Dietary PZ + PP tended to increase the jejunal villus height (VH) of weaned piglets (p = 0.055), and significantly increased the villus-height-to-crypt-depth ratio compared to the NC group (p < 0.05). (3) Compared with the NC group, PZ supplementation decreased the relative abundance of Firmicutes and increased the relative abundance of Bacteroidetes, and the relative abundance of Lactobacillus in the PZ and PZ + PP groups were both increased. In conclusion, porous zinc oxide and plant polyphenols may have synergistic effects in modulating intestinal health in weaned piglets and be a potential alternative to high-dose zinc oxide.
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BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.
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Úlcera Péptica Hemorrágica , Humanos , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Péptica Hemorrágica/classificação , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Inteligência Artificial , Redes Neurais de Computação , Curva ROC , Estudos Prospectivos , Idoso , Gravação em Vídeo , Gastroscopia/métodos , Reprodutibilidade dos Testes , AdultoRESUMO
Graphene oxide (GO) is an oxidized form of graphene-based materials with abundant hydrophilic oxygen-containing functional groups, forming well-dispersed suspensions and serving as pollution carriers. The natural anaerobic environment might alter the sorption behavior of GO, which in turn affects the fate and bioavailability of GO-sorbed organic contaminants. In this study, GO can be reduced by diverse environmental reductants, including sodium sulfide, DL-1,4-dithiothretiol, and L-cysteine, forming aggregates. Meanwhile, the GO-sorbed organic contaminants were released during the reduction process owing to the decreasing oxygen content and sorption sites. The effect of solution chemistry conditions (dissolved humic acid/HA and ionic strength) on the reduction release process was also investigated. HA reduced the release rate of organic contaminants due to its stabilization effect. Adding NaCl did not alter the release rate, while CaCl2 markedly enhanced the release rate. Toxicity tests with Bacillus subtilis indicated that releasing the pre-sorbed organic compound on GO led to a lower survival ratio and enhanced the superoxide dismutase activity. The findings of this study imply that the anaerobic environment could alter the dispersion/aggregation status of GO, affecting the sorption interaction between GO and the organic compounds and consequently influencing the toxicity and risk of pollution in the environment.
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Grafite , Grafite/química , Óxidos/química , Anaerobiose , OxigênioRESUMO
OBJECTIVES: Pan-immune-inflammation value (PIV) is defined by the neutrophil, platelet, monocyte, and lymphocyte counts and is associated with immune-checkpoint inhibitor (ICI) therapy outcomes in advanced non-small cell lung cancer (aNSCLC). However, PIV is dynamic under therapy and its longitudinal assessment may help predict efficacy. This study investigated the impact of baseline PIV and its dynamics on ICI efficacy and its immune-related adverse events (irAEs). The study additionally attempted to understand the biological significance of PIV. PATIENTS AND METHODS: This retrospective study analyzed the clinical data of 269 consecutive patients with aNSCLC. PIV was calculated at baseline and at weeks 3-4 to determine its association with overall survival (OS), progression-free survival (PFS), and irAEs. RESULTS: Results revealed that low baseline PIV was positively correlated with the incidence of irAEs. Moreover, a low PIV at baseline was significantly associated with a prolonged PFS (median PFS: 10 vs. 7 months, p = 0.0005) and OS (median OS: 29 vs. 21 months, p < 0.0001). When the PIV at baseline and weeks 3-4 was considered together, its low dynamics correlated with a higher incidence of irAEs (p = 0.001), a longer PFS (median PFS, 9 vs. 6 months, p = 0.012), and a longer OS (median OS; 28 vs. 21 months, p = 0.002). CONCLUSION: Thus, PIV at baseline and its dynamics are novel and potent predictors of irAEs, PFS, and OS in patients with aNSCLC receiving immunotherapy. Moreover, the PIV dynamics may be an effective, novel surrogate marker to dynamically observe the efficacy of immunotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Imunoterapia/efeitos adversos , Imunoterapia/métodosRESUMO
Lithium-selenium batteries are characterized by high volumetric capacity comparable to Li-S batteries, while ≈1025 times higher electrical conductivity of Se than S is favorable for high-rate capability. However, they also suffer from the "shuttling effect" of lithium polyselenides (LPSes) and Li dendrite growth. Herein, a multifunctional Janus separator is designed by coating hierarchical nitrogen-doped carbon nanocages (hNCNC) and AlN nanowires on two sides of commercial polypropylene (PP) separator to overcome these hindrances. At room temperature, the Li-Se batteries with the Janus separator exhibit an unprecedented high-rate capability (331 mAh g-1 at 25 C) and retain a high capacity of 408 mAh g-1 at 3 C after 500 cycles. Moreover, the high retained capacities are achieved over a wide temperature range from -30 °C to 60 °C, showing the potential application under extreme environments. The excellent performances result from the "1+1>2" synergism of suppressed LPSes shuttling by chemisorption and electrocatalysis of hNCNC on the cathode side and suppressed Li-dendrite growth by thermally conductive AlN-network on the anode side, which can be well understood by the "Bucket Effect". This Janus separator provides a general strategy to develop high-performance lithium-chalcogen (Se, S, SeS2 ) batteries.
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Trace metals (TRs) and polycyclic aromatic hydrocarbons (PAHs) are major toxic components of fine particulate matter (PM2.5) and related to various health adverse outcomes. The study aims to get a better understanding of the contents, sources and risks of PM2.5-bounded TRs and PAHs in Hefei, China, during the period of 2019-2021. We collected 504 samples and measured twelve TRs and sixteen priority PAHs by inductively coupled plasma mass spectrometry and high-performance liquid chromatography. The annual mass concentrations of PM2.5 was fluctuated in the year of 2019-2021 at 50.95, 47.48 and 59.38 µg/m3, with seasonal variations in rank order of winter > spring > autumn > summer. The median concentrations of PM2.5-bounded Æ©TRs and Æ©PAHs were also fluctuated, 132.85, 80.93 and 120.27 ng/m3 for Æ©TRs, 2.57, 5.85 and 2.97 ng/m3 for Æ©PAHs, in the year of 2019, 2020 and 2021, respectively. Seasonal variations of Æ©TRs and Æ©PAHs show the highest concentration in winter. Positive matrix factorization was used for identified pollution emission sources, and TRs mainly originated from coal combustion, traffic emission and fugitive dust, while PAHs stemmed from biomass, diesel, gasoline and coal combustion. Health risk assessment indicated that adults were more vulnerable than children, the carcinogenic risk assessment of As and Cr manifested a certain degree of cancer risk (1.0 × 10-6 < CR < 1.0 × 10-4) in adults group, and health risks of TRs were higher than PAHs in Hefei. These findings suggest that PM2.5-bounded TRs and PAHs should be considered when making emission control strategies for air pollution, and winter, combustion sources and adults should achieve more policy attention to decrease exposure risks in Hefei.
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Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Oligoelementos , Adulto , Criança , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Material Particulado/análise , Estações do Ano , Medição de Risco , China , Oligoelementos/análise , Monitoramento Ambiental/métodos , Carvão Mineral/análiseRESUMO
Cysteine is a critically important amino acid necessary for mammalian cell culture, playing key roles in nutrient supply, disulfide bond formation, and as a precursor to antioxidant molecules controlling cellular redox. Unfortunately, its low stability and solubility in solution make it especially problematic as an essential medium component that must be added to Chinese hamster ovary and other mammalian cell cultures. Therefore, CHO cells have been engineered to include the capacity of endogenously synthesizing cysteine by overexpressing multiple enzymes, including cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CTH) and glycine N-methyltransferase (GNMT) to reconstruct the reverse transsulfuration pathway and overcome a key metabolic bottleneck. Some limited cysteine biosynthesis was obtained by overexpressing CBS and CTH for converting homocysteine to cysteine but robust metabolic synthesis from methionine was only possibly after incorporating GNMT which likely represents a key bottleneck step in the cysteine biosynthesis pathway. CHO cells with the reconstructed pathway exhibit the strong capability to proliferate in cysteine-limited and cysteine-free batch and fed-batch cultures at levels comparable to wildtype cells with ample cysteine supplementation, providing a selectable marker for CHO cell engineering. GNMT overexpression led to the accumulation of sarcosine byproduct, but its accumulation did not affect cell growth. Furthermore, pathway reconstruction enhanced CHO cells' reduced and glutathione levels in cysteine-limited conditions compared to unmodified cells, and greatly enhanced survivability and maintenance of redox homeostasis under oxidative stress induced by addition of menadione in cysteine-deficient conditions. Such engineered CHO cell lines can potentially reduce or even eliminate the need to include cysteine in culture medium, which not only reduces the cost of mammalian media but also promises to transform media design by solving the challenges posed by low stability and solubility of cysteine and cystine in future mammalian biomanufacturing processes.
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Aminoácidos , Estresse Oxidativo , Cricetinae , Animais , Cricetulus , Células CHO , Aminoácidos/metabolismo , Cistationina beta-Sintase/metabolismo , Cisteína/genética , Cisteína/metabolismoRESUMO
Methyltransferase-like protein 7A (METTL7A), an RNA N6-methyladenosine (m6A) methyltransferase, has attracted much attention as it has been found to be closely associated with various types of tumorigenesis and progression. This study provides a comprehensive assessment of METTL7A from a pan-cancer perspective using multi-omics data. The gene ontology enrichment analysis of METTL7A-binding proteins revealed a close association with methylation and lipid metabolism. We then explored the expression of METTL7A in normal tissues, cell lines, different subtypes and cancers, and found that METTL7A was differentially expressed in various cancer species, tumor molecular subtypes and immune subtypes. Evaluation of the diagnostic and prognostic value of METTL7A in pan-cancer revealed that METTL7A had high accuracy in tumor prediction. Moreover, the low expression of METTL7A significantly correlated with the poor prognosis, including kidney renal clear cell carcinoma (KIRC), mesothelioma and sarcoma, indicating that METTL7A could be a potential biomarker for tumor diagnosis and prognosis. We focused on KIRC after pre-screening and analyzed its expression and prognostic value in various clinical subgroups. We found that METTL7A was significantly related to tumor stage, metastasis stage, pathologic stage, primary therapy outcome, histologic grade and gender, and that low METTL7A expression was associated with poorer outcomes. Finally, we analyzed the immune infiltration and co-expressed genes of METTL7A as well as the differentially expressed genes in the high and low expression groups. In conclusion, METTL7A is a better molecular marker for pan-cancer diagnosis and prognosis and has high potential as a diagnostic and prognostic biomarker for KIRC.
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Carcinoma de Células Renais , Neoplasias Renais , Mesotelioma , Sarcoma , Humanos , Multiômica , BiomarcadoresRESUMO
In this research, the treatment of methylene blue (MB) dye wastewater by a novel system that combines H2O2 with an aluminum-carbon micro-electrolysis (ACE) was explored. The effects of the H2O2 amount, initial pH, aluminum to carbon ratio, total aluminum-carbon mass, dye concentration, and reaction temperature on degradation of MB were investigated. The findings revealed that under the following conditions: H2O2 34.0 mg/L, initial pH of 3.0, aluminum-to-carbon ratio of 2:1, total aluminum-carbon mass of 2.0 g/L, MB concentration of 20 mg/L, and 20 °C, the degradation rate of MB could reach 99.3% after 180 min, which is 18.4% more compared with ACE at the same conditions without H2O2. Through the quenching experiments, it was proved that the efficient free radicals produced during degradation are â¢OH and â¢O2-. Finally, a possible mechanism of H2O2 enhanced aluminum carbon micro-electrolysis (HP-ACE) for MB degradation was discussed.
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Águas Residuárias , Poluentes Químicos da Água , Alumínio , Carbono , Corantes , Eletrólise , Peróxido de Hidrogênio , Azul de Metileno , Eliminação de Resíduos LíquidosRESUMO
INTRODUCTION AND OBJECTIVES: Necroptosis and endoplasmic reticulum (ER) stress has been implicated in acute and chronic liver injury. Activated eukaryotic initiation factor 2 alpha (eIF2α) attenuates protein synthesis and relieves the load of protein folding in the ER. In this study, we aimed to analyze the impact of eIF2α phosphorylation on hepatocyte necroptosis in acute liver injury. MATERIALS AND METHODS: Male BALB/c mice were injected with tunicamycin or d-galactosamine, and LO2 cells were incubated with tunicamycin to induce acute liver injury. 4-Phenylbutyric acid (PBA) and salubrinal were used to inhibit ER stress and eIF2α dephosphorylation, respectively. We analyzed the eIF2α phosphorylation, ER stress, and hepatocyte necroptosis in mice and cells model. RESULTS: Tunicamycin or d-galactosamine significantly induced ER stress and necroptosis, as well as eIF2α phosphorylation, in mice and LO2 cells (p<0.05). ER stress aggravated tunicamycin-induced hepatocyte necroptosis in mice and LO2 cells (p<0.05). Elevated eIF2α phosphorylation significantly mitigated hepatocyte ER stress (p<0.05) and hepatocyte necroptosis in mice (34.37±3.39% vs 22.53±2.18%; p<0.05) and LO2 cells (1±0.11 vs 0.33±0.05; p<0.05). Interestingly, tumor necrosis factor receptor (TNFR) 1 protein levels were not completely synchronized with necroptosis. TNFR1 expression was reduced in d-galactosamine-treated mice (p<0.05) and cells incubated with tunicamycin for 12 and 24h (p<0.05). ER stress partially restored TNFR1 expression and increased necroptosis in tunicamycin-incubated cells (p<0.05). CONCLUSIONS: These results imply that ER stress can mediate hepatocyte necroptosis independent of TNFR1 signaling and elevated eIF2α phosphorylation can mitigate ER stress during acute liver injury.
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Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Fator de Iniciação 2 em Eucariotos/metabolismo , Hepatócitos/metabolismo , Necroptose/fisiologia , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Animais , Antibacterianos/toxicidade , Western Blotting , Linhagem Celular , Sobrevivência Celular , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cinamatos/farmacologia , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Galactosamina/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Técnicas In Vitro , Camundongos , Necroptose/efeitos dos fármacos , Fenilbutiratos/farmacologia , Fosforilação , Tioureia/análogos & derivados , Tioureia/farmacologia , Tunicamicina/toxicidadeRESUMO
HYPOTHESIS: A superhydrophilic membrane with rough and hierarchical structures is possibly fouled by surfactant-stabilized oil and organic foulants, because these foulants could not be hindered by the water layer formed on superhydrophilic membrane surface. A dynamic membrane was possibly an effective method to address this fouling problem. EXPERIMENTS: A microfiltration membrane, a nanofiber membrane, and a dynamic membrane were used for the separation of surfactant-free emulsions, surfactant-stabilized emulsions, and the surfactant-stabilized emulsions containing typical organic foulants. The oil rejection and membrane fouling were compared. FINDINGS: The microfiltration membrane, nanofiber membrane, and dynamic membrane had high resistances to the fouling by surfactant-free emulsions because these membranes were underwater superoleophobic. However, these membranes showed low resistances to the fouling by surfactant-stabilized oil droplets and organic foulants. For the dynamic membrane, the oil droplets and organic foulants trapped in the separation layer could be readily removed in the detachment-washing-recoating steps; therefore, almost no physically irreversible fouling was observed in the multi-cycle filtration. With the size distributions of oil droplets in the emulsions and the particle of the dynamic membrane, the rejection of oil by the dynamic membrane could be calculated by simply assuming that the particle was spherical, uniform, and tightly packed.
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With the current biotherapeutic market dominated by antibody molecules, bispecific antibodies represent a key component of the next-generation of antibody therapy. Bispecific antibodies can target two different antigens at the same time, such as simultaneously binding tumor cell receptors and recruiting cytotoxic immune cells. Structural diversity has been fast-growing in the bispecific antibody field, creating a plethora of novel bispecific antibody scaffolds, which provide great functional variety. Two common formats of bispecific antibodies on the market are the single-chain variable fragment (scFv)-based (no Fc fragment) antibody and the full-length IgG-like asymmetric antibody. Unlike the conventional monoclonal antibodies, great production challenges with respect to the quantity, quality, and stability of bispecific antibodies have hampered their wider clinical application and acceptance. In this review, we focus on these two major bispecific types and describe recent advances in the design, production, and quality of these molecules, which will enable this important class of biologics to reach their therapeutic potential.
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Nitroaromatic compounds (NACs) are widely distributed in the environment and are considered toxic or carcinogenic. However, little attention has been paid to the binding interactions between NACs and biomacromolecules (e.g., proteins). Here we investigated the effects of three model NACs, nitrobenzene (NB), 1,3-dinitrobenzene (DNB), and 1,3,5-trinitrobenzene (TNB), on the activity of acetylcholinesterase (AChE). The presence of NACs (up to 0.5â¯mM) effectively suppressed the AChE-catalyzed hydrolysis of acetylthiocholine iodide, with the suppression effect increasing with the nitro-group substitution (TNBâ¯>â¯DNBâ¯>â¯NB). Consistently, the UV absorption of AChE at 206â¯nm arising from the skeleton structure decreased by the addition NACs, and the decrease exhibited the same compound sequence, reflecting the perturbing interactions with the skeleton enzyme structure. However, no changes were made on the secondary structure of AChE, as evidenced by the circular dichroism analysis. The fluorescence quenching analysis of AChE demonstrated that NB and DNB interacted with both tryptophan (Trp) and tyrosine (Tyr) residues, whereas TNB interacted only with Trp. The UV absorption and fluorescence quenching analyses both reflected that the interactions with the non-skeleton aromatic amino acids were weak. 1H NMR analysis confirmed the strong π-π coupling interactions between TNB and model Trp. Molecular simulation indicated that the DNB or TNB molecule was sandwiched between Trp84 and Phe330 at the catalytic site via π-π coupling interactions. The findings highlight the importance of specific interactions of NACs with proteins to cause them to malfunction.
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Acetilcolinesterase/química , Análise Espectral/métodos , Modelos MolecularesRESUMO
With increasing use of organophosphate esters (OPEs) largely due to the phasing out of various brominated flame retardants, much more attention has been paid to their occurrence, distribution and potential health risks. In this study, we investigated the occurrence and distribution characteristics associated to their potential health risks of selected 13 OPEs in outdoor dust with a comparison between urban and rural areas in Nanjing, China as well as seasonal variations. Ten out of 13 OPEs showed higher concentrations in urban dust than those in rural dust (pâ¯<â¯0.05). Six OPEs congeners exhibited significantly different concentrations with seasonal variations (pâ¯<â¯0.01) in rural dust. Halogenated OPEs were the dominant group in both urban (median: 56.8%) and rural (median: 45.9%) dust, and tris(2-chloroisopropyl) phosphate (TCPP) was found to be the most abundant OPE in both urban (median: 48.7%) and rural (median:26.4%) dust. Principal component analysis with multiple linear regression (PCA-MLR) and spearman correlations showed the different sources of OPEs in urban and rural dust. The non-carcinogenic (Hazard Index, HIâ¯<â¯1.62â¯×â¯10-5) and carcinogenic risks (CRâ¯<â¯2.28â¯×â¯10-9) of ΣOPEs were much lower than the theoretical threshold of risk, revealing a negligible risk to local residents from the exposure of OPEs in outdoor dust.
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Poeira/análise , Monitoramento Ambiental , Ésteres/análise , Retardadores de Chama/análise , Organofosfatos/análise , China , Humanos , Medição de Risco , População Rural , Estações do Ano , População UrbanaRESUMO
Synthesized iron oxychloride (FeOCl) was firstly applied to activate peroxymonosulfate (PMS) to degrade imipramine (IMI), a tricyclic antidepressant. Compared to some other Fe-based materials including zero valent iron, Fe2O3, Fe3O4 and ferric ions, FeOCl presented an impressive catalytic activity on PMS at near-neutral condition due to its unique structure containing abundant unsaturated iron atoms and oxo-bridged configuration. With an increase of FeOCl dose, PMS dose or initial pH in ranges of 0.02â¯-â¯0.5â¯g/L, 0.1â¯-â¯2.5â¯mM and 4.0â¯-â¯8.0, the degradation efficiency of IMI was effectively raised by 64.0%, 48.5% and 50.6%, respectively. The presence of either bicarbonate or chloride stimulated the removal of IMI. Moreover, 70.4% of IMI was degraded under the background of real water with 2â¯mM PMS. The possible reactive species were identified as sulfate and hydroxyl radicals. The formed hypochlorite through the reaction of PMS and the released chloride ions may also contribute to the degradation of IMI. Among the oxidants, sulfate radical was proven to be the dominate one in the system. Additionally, the FeOCl/PMS system can overall effectively degrade six other organic compounds including amitriptyline, desipramine, propranolol, nitrobenzene, methyl-paraben and ethyl-paraben, further suggesting the possible application of this system in treatment of vast aquatic micro-organic pollutants.
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Antidepressivos Tricíclicos/química , Imipramina/química , Compostos de Ferro/química , Oxidantes/química , Peróxidos/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Catálise , OxirreduçãoRESUMO
PURPOSE: The purpose of the study is to monitor the exposure and health of workers in Great Britain who use pesticides as a part of their job, and to gain a better understanding of the relationship between long-term exposure to pesticides and health. PARTICIPANTS: Study participants are professional pesticide users who are certified in the safe use of pesticides or who were born before 1965 and apply pesticides under 'grandfather rights'. Overall response rate was 20%; participants are mostly male (98%) and the average age is 54 years, ranging from 17 to over 80 years. FINDINGS TO DATE: Participants have completed a baseline general questionnaire and three follow-up questionnaires on the use of pesticides. These data will enable investigations into the relationship between occupational pesticide exposure and health outcomes taking into account non-occupational confounding factors. FUTURE PLANS: There is no set end date for data collection. Recruitment into the cohort will continue, and for the foreseeable future there will be annual pesticide use questionnaires and five yearly follow-up general questionnaires.The intention is to validate the pesticide use questionnaire, and to develop a crop/job exposure matrix (C/JEM) which can be updated regularly. This C/JEM will be able to look at general categories of pesticide, such as insecticides, structurally related pesticides, such as organochlorines, or individual active ingredients. Data collected on use of personal protective equipment and method of application will provide information on how potential exposure to pesticide during application may have been modified. The study will be able to estimate changes in individual pesticide use over time, and to examine the associations between pesticide use and both baseline and long-term health outcomes.The cohort members will be linked to national databases for notification of hospital episode statistics, cancer incidence and mortality for follow-up of health outcomes.
Assuntos
Agricultura , Exposição Ocupacional , Ocupações , Praguicidas/farmacologia , Trabalho , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Emprego , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Praguicidas/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Reino Unido , Adulto JovemRESUMO
AIMS: Analyze relationships between adherence to guidelines for diabetes care - regular screening; physical activity; and medication - and diabetes complications and mortality. METHODS: Outcomes were onset of congestive heart failure (CHF), stroke, renal failure, moderate complications of lower extremities, lower-limb amputation, proliferative diabetic retinopathy (PDR), and mortality during follow-up. Participants were persons aged 65+ in the Health and Retirement Study (HRS) 2003 Diabetes Study and had Medicare claims in follow-up period (2004-8). RESULTS: Adherence to screening recommendations decreased risks of developing CHF (odds ratio (OR)=0.83; 95% confidence interval (CI): 0.72-0.96), stroke (OR=0.80; 95% CI: 0.68-0.94); renal failure (OR=0. 82; 95% CI: 0.71-0.95); and death (OR=0.86; 95% CI: 0.74-0.99). Adherence to physical activity recommendation reduced risks of stroke (OR=0.64; 95% CI: 0.45-0.90), renal failure (OR=0.71; 95% CI: 0.52-0.97), moderate lower-extremity complications (OR=0.71; 95% CI: 0.51-0.99), having a lower limb amputation (OR=0.31, 95% CI: 0.11-0.85), and death (OR=0.56, 95% CI: 0.41-0.77). Medication adherence was associated with lower risks of PDR (OR=0.35, 95% CI: 0.13-0.93). CONCLUSIONS: Adherence to screening, physical activity and medication guidelines was associated with lower risks of diabetes complications and death. Relative importance of adherence differed among outcome measures.
Assuntos
Complicações do Diabetes/prevenção & controle , Diabetes Mellitus/terapia , Promoção da Saúde , Cooperação do Paciente , Guias de Prática Clínica como Assunto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/mortalidade , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Diagnóstico Precoce , Feminino , Inquéritos Epidemiológicos , Humanos , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Programas de Rastreamento , Medicare Part A , Medicare Part B , Adesão à Medicação , Atividade Motora , Risco , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To examine disability trends among U.S. near-elderly and elderly persons and explain observed trends. DATA SOURCE: 1996-2010 waves of the Health and Retirement Study. STUDY DESIGN: We first examined trends in Activities of Daily Living and Instrumental Activities of Daily Living limitations, and large muscle, mobility, gross motor, and fine motor indexes. Then we used decomposition analysis to estimate contributions of changes in sociodemographic composition, self-reported chronic disease prevalence and health behaviors, and changes in disabling effects of these factors to disability changes between 1996 and 2010. PRINCIPAL FINDINGS: Disability generally increased or was unchanged. Increased trends were more apparent for near-elderly than elderly persons. Sociodemographic shifts tended to reduce disability, but their favorable effects were largely offset by increased self-reported chronic disease prevalence. Changes in smoking and heavy drinking prevalence had relatively minor effects on disability trends. Increased obesity rates generated sizable effects on lower-body functioning changes. Disabling effects of self-reported chronic diseases often declined, and educational attainment became a stronger influence in preventing disability. CONCLUSIONS: Such unfavorable trends as increased chronic disease prevalence and higher obesity rates offset or outweighed the favorable effects with the result that disability remained unchanged or increased.