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A flexible, tough, highly transparent and piezoelectric polyacrylamide hydrogel was fabricated induced by blue light photocuring, with camphorquinone/diphenyliodonium hexafluorophosphate (CQ/DPI) as the blue light initiator, acrylamide (AM) and N,N-dimethylacrylamide (DMAA) as monomers, polyethylene glycol diacrylate (PEGDA) as the crosslinker, lecithin as the dispersant, and BaTiO3 as the piezoelectric material. Various performance tests were carried out on the hydrogel, and the results showed that lecithin enhances the dispersion of BaTiO3 within the system and improves the tensile properties (>100% strain) of the hydrogel, and the addition of PEGDA not only improves the photopolymerization performance of the hydrogel, but also significantly improves its fracture strength (â¼0.3 MPa). In addition, BaTiO3 enables the resultant hydrogels to show excellent conductivity (>1.5) and stable response to strain. The assembled hydrogel sensor shows a sensitive response to human joint activities, which is expected to be applied in self-powered sensors and energy collection.
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BACKGROUND: Burnout among health care professionals is a significant concern, with detrimental effects on health care service quality and patient outcomes. The use of the electronic health record (EHR) system has been identified as a significant contributor to burnout among health care professionals. OBJECTIVE: This systematic review and meta-analysis aims to assess the prevalence of burnout among health care professionals associated with the use of the EHR system, thereby providing evidence to improve health information systems and develop strategies to measure and mitigate burnout. METHODS: We conducted a comprehensive search of the PubMed, Embase, and Web of Science databases for English-language peer-reviewed articles published between January 1, 2009, and December 31, 2022. Two independent reviewers applied inclusion and exclusion criteria, and study quality was assessed using the Joanna Briggs Institute checklist and the Newcastle-Ottawa Scale. Meta-analyses were performed using R (version 4.1.3; R Foundation for Statistical Computing), with EndNote X7 (Clarivate) for reference management. RESULTS: The review included 32 cross-sectional studies and 5 case-control studies with a total of 66,556 participants, mainly physicians and registered nurses. The pooled prevalence of burnout among health care professionals in cross-sectional studies was 40.4% (95% CI 37.5%-43.2%). Case-control studies indicated a higher likelihood of burnout among health care professionals who spent more time on EHR-related tasks outside work (odds ratio 2.43, 95% CI 2.31-2.57). CONCLUSIONS: The findings highlight the association between the increased use of the EHR system and burnout among health care professionals. Potential solutions include optimizing EHR systems, implementing automated dictation or note-taking, employing scribes to reduce documentation burden, and leveraging artificial intelligence to enhance EHR system efficiency and reduce the risk of burnout. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021281173; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021281173.
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The bean flower thrip Megalurothrips usitatus (Bagnall) is a severe pest on cowpeas and causes a 20-30% reduction in cowpeas in Hainan, China, with even complete crop failure in severe cases. Spinetoram is currently the most important pesticide against M. usitatus in cowpea production. In the main producing areas of cowpeas in Hainan, however, the efficacy of spinetoram against M. usitatus is not well known. In the present study, we employed the maximum dose bioassay to evaluate the efficacy of the mortality rates of adult thrips at F0 in spinetoram, freshly collected from 212 field populations of M. usitatus collected from 20 villages in the Yazhou District of Hainan. Our results showed that the mortality rates of these thrip populations exposed to spinetoram were from 3.31% to 100%. Among them, the mortality rates of 66.98% (142/212) of the populations exceeded 80%, while that of 33.96% (72/212) of the populations surpassed 90%. Only a small proportion of 0.47% (1/212) the populations exhibited a mortality rate below 10%, and 4.72% (10/212) displayed rates below 50%. Furthermore, significant differences were also observed in the mortality rates of thrips among different villages. Taken together, the maximum dosage bioassay method is a rapid and easily implemented approach providing valuable insights into the field efficacy of insecticides and offers guidance in determining the optimal dosage required in the field. Spinetoram is still effective against M. usitatus in the main producing areas of cowpeas in Hainan, but caution should be exercised in its combined use with other methods to reduce potential resistance.
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As a central component for anion exchange membrane fuel cells (AEMFCs), the anion exchange membrane is now facing the challenge of further improving its conductivity and alkali stability. Herein, a twisted all-carbon backbone is designed by introducing stereo-contorted units with piperidinium groups dangled at the twisted sites. The rigid and twisted backbone improves the conduction of hydroxide and brings down the squeezing effect of the backbone on piperidine rings. Accordingly, an anion exchange membrane prepared through this method exhibits adapted OH- conductivity, low swelling ratio and excellent alkali stability, even in high alkali concentrations. Further, a fuel cell assembled with a such-prepared membrane can reach a power density of 904.2 mW/cm2 and be capable of continuous operation for over 50 h. These results demonstrate that the designed membrane has good potential for applications in AEMFCs.
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Engineering bacteria are considered as a potential treatment for cardiovascular diseases and related risk factors. Oral bacteria are closely related to the occurrence and development of cardiovascular diseases, and their engineering has broad prospects and potential in the treatment of cardiovascular diseases. Oral pathogenic bacteria undergo protein and genetic engineering, including the incorporation of exogenous plasmids to yield therapeutic effects; genetically engineered oral probiotics can be harnessed to secrete cytokines and reactive oxygen species, offering novel therapeutic avenues for cardiovascular diseases.
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Macrophages play pivotal roles in the regulation of inflammatory responses and tissue repair, making them a prime target for inflammation alleviation. However, the accurate and efficient macrophages targeting is still a challenging task. Motivated by the efficient and specific removal of apoptotic cells by macrophages efferocytosis, a novel biomimetic liposomal system called Effero-RLP (Efferocytosis-mediated Red blood cell hybrid Liposomes) is developed which incorporates the membrane of apoptotic red blood cells (RBCs) with liposomes for the purpose of highly efficient macrophages targeting. Rosiglitazone (ROSI), a PPARγ agonist known to attenuate macrophage inflammatory responses, is encapsulated into Effero-RLP as model drug to regulate macrophage functions in DSS-induced colitis mouse model. Intriguingly, the Effero-RLP exhibits selective and efficient uptake by macrophages, which is significantly inhibited by the efferocytosis blocker Annexin V. In animal models, the Effero-RLP demonstrates rapid recognition by macrophages, leading to enhanced accumulation at inflammatory sites. Furthermore, ROSI-loaded Effero-RLP effectively alleviates inflammation and protects colon tissue from injury in the colitis mouse model, which is abolished by deletion of macrophages from mice model. In conclusion, the study highlights the potential of macrophage targeting using efferocytosis biomimetic liposomes. The development of Effero-RLP presents novel and promising strategies for alleviating inflammation.
Subject(s)
Drug Delivery Systems , Inflammation , Liposomes , Macrophages , Animals , Mice , Biomimetics/methods , Colitis/drug therapy , Colitis/metabolism , Disease Models, Animal , Drug Delivery Systems/methods , Efferocytosis/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Macrophages/metabolism , Macrophages/drug effects , Mice, Inbred C57BL , Rosiglitazone/pharmacologyABSTRACT
Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.
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Background: Lactoferrin (LF) is a multifunctional glycoprotein found in human milk and body fluids, which has been shown to play a vital role in regulating the immunity and supporting the intestinal health of infants. Aim: This study evaluated the association between maternal/parturient factors and LF concentration in the breast milk of Chinese mothers. Methods: 207 breast milk samples were collected from healthy mothers with in the first year of lactation. Maternal and parturient information was collected for these participants through questionnaires. The content of lactoferrin in breast milk was detected by liquid chromatography, and macronutrient concentration in breast milk was measured by human milk analyzer in only 109 samples. Results: Our findings demonstrated that the LF content was much higher within the first month of lactation than it was after that period (p < 0.05). When compared with normal and lean mothers, the LF content of obese mothers was considerably higher (p < 0.05). The parity and LF content showed a favorable correlation. The proportion of LF to total protein tended to decrease as lactation progressed. Protein, fat, dry matter, and energy content were significantly positively correlated with LF content (p < 0.001). Conclusion: Early breast milk tends to have a higher level of LF, and the change of LF concentration in breast milk is associated with the parity and body mass index of the mother.
Subject(s)
Lactoferrin , Milk, Human , Pregnancy , Infant , Female , Humans , Milk, Human/chemistry , Lactoferrin/analysis , Body Mass Index , Breast Feeding , Lactation/physiology , ParityABSTRACT
LC3-associated phagocytosis (LAP) is an instrumental machinery for the clearance of extracellular particles including apoptotic cells for the alleviation of inflammation. While pharmacological approaches to modulate LAP for inflammation regulation have been poorly explored, in our study we identified a novel compound, columbamine (COL), which can trigger LAP and enhance efferocytosis in an animal model of colitis to attenuate inflammation. We found that COL directly binds to and biasedly activates FPR2 (formyl peptide receptor 2) to promote efferocytosis and alleviate colitis. Biochemically, COL induces an interaction between RAC1 and the PIK3C3/VPS34-RUBCN/RUBICON complex, stimulating LC3-associated efferocytosis. These findings provide a novel interpretation of the potential roles of LAP in regulating inflammatory bowel disease (IBD), reveal the relationship between G protein-coupled receptors (GPCRs) and LAP, and highlight the role of RAC1 in regulating the PIK3C3/VPS34-RUBCN complex in LAP.
Subject(s)
Colitis , Inflammation , Phagocytosis , rac1 GTP-Binding Protein , Animals , Phagocytosis/drug effects , rac1 GTP-Binding Protein/metabolism , Inflammation/pathology , Humans , Colitis/pathology , Colitis/metabolism , Mice , Microtubule-Associated Proteins/metabolism , Receptors, Formyl Peptide/metabolism , Mice, Inbred C57BL , Receptors, Lipoxin/metabolism , Intestines/pathology , EfferocytosisABSTRACT
Autophagy is a highly conserved physiological process that maintains cellular homeostasis by recycling cellular contents. Selective autophagy is based on the specificity of cargo recognition and has been implicated in various human diseases, including neurodegenerative diseases and cancer. Selective autophagy receptors and modulators play key roles in this process. Identifying these receptors and modulators and their roles is critical for understanding the machinery and physiological function of selective autophagy and providing therapeutic value for diseases. Using modern researching tools and novel screening technologies, an increasing number of selective autophagy receptors and modulators have been identified. A variety of Strategies and approaches, including protein-protein interactions (PPIs)-based identification and genome-wide screening, have been used to identify selective autophagy receptors and modulators. Understanding the strengths and challenges of these approaches not only promotes the discovery of even more such receptors and modulators but also provides a useful reference for the identification of regulatory proteins or genes involved in other cellular mechanisms. In this review, we summarize the functions, disease association, and identification strategies of selective autophagy receptors and modulators.
Subject(s)
Autophagy , Humans , Autophagy/genetics , HomeostasisABSTRACT
Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage-mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3-associated phagocytosis (LAP), a non-canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G-protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL-induced efferocytosis, anti-colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3-associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.
Subject(s)
Colitis , Mice , Animals , Phagocytosis , Signal Transduction , Inflammation/genetics , Macrophages/metabolism , Colitis/metabolismABSTRACT
BACKGROUND: Lung cancer patients with coronavirus disease 2019 (COVID-19) infection experience high mortality rates. The study aims to determine the risk factors for mortality in lung cancer patients with COVID-19 infection. MATERIALS AND METHODS: Followed the PRISMA reporting guidelines, PubMed, Embase, and Web of Science were systematically searched to February 20, 2023, for studies of lung cancer patients with COVID-19 infection. The main outcome of interest was the risk factor for mortality. We also compared the mortality rate of those patients among different continents. A pooled risk ratio (RR) with 95% CI was presented as the result of this meta-analysis. RESULTS: Meta-analysis of 33 studies involving 5018 patients showed that pooled mortality rate of lung cancer in COVID-19 patients was 0.31 (95% CI: 0.25-0.36). Subgroup analysis based on the continents showed significant difference of the mortality rate was observed between Asia and the rest of world (χ2 = 98.96, P < 0.01). Older age (SMD: 0.24, 95% CI: 0.09-0.40, P < 0.01), advanced lung cancer (RR: 1.14, 95% CI: 1.04-1.26, P < 0.01), coexisting comorbidities such as hypertension (RR: 1.17, 95% CI: 1.01-1.35, P = 0.04) and cardiovascular disease (RR: 1.40, 95% CI: 1.03-1.91, P = 0.03) were associated with higher risk of mortality rate in those patients. CONCLUSIONS: Findings of this meta-analysis confirms an increased risk of mortality in lung cancer patients with COVID-19 infection, whose risk factors for these patients appear to be exacerbated by older age, advanced-stage lung cancer, and comorbidities such as hypertension and cardiovascular disease.
Subject(s)
COVID-19 , Cardiovascular Diseases , Hypertension , Lung Neoplasms , Humans , COVID-19/complications , Lung Neoplasms/complications , Risk Factors , Hypertension/complicationsABSTRACT
AIM: The association between composite dietary antioxidant index (CDAI) and hypertension remains unknown. Our study was to investigate the association of CDAI with hypertension in general adults. METHODS: A total of 21 526 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). The CDAI was calculated from the intake of six dietary antioxidants. Multivariable logistic regressions were performed to explore the associations between CDAI and the prevalence of hypertension. Non-linear correlations were explored using restricted cubic splines. And the inflection point was determined by the two-piecewise linear regression. RESULTS: In the multivariate logistic regression model with full adjustment for confounding variables, the odds ratio (95% confidence interval) of CDAI associating with hypertension was 0.98 (0.97-1.00; P = .016). Besides, compared to the lowest quartile, the highest quartile of CDAI was associated with a lower risk of hypertension (0.81 [0.70-0.94]; P = .006). Furthermore, a linear association was found by restricted cubic spline, with 3.4 being the turning point. CONCLUSION: Our study highlighted a negative linear association between CDAI and hypertension in general adults.
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Antioxidants , Hypertension , Adult , Humans , Nutrition Surveys , Diet , Hypertension/epidemiology , Hypertension/etiologyABSTRACT
Solar-assisted interfacial evaporation is a promising approach for purifying and desalinating water. As a sustainable biomass material, wood has attracted increasing interest as an innovative substrate for solar desalination, owing to its intrinsic porous structure, high hydrophilicity, and low thermal conductivity. However, developing wood-based solar evaporators with high evaporation rates and excellent salt resistance still remains a significant challenge, owing to the absence of large pores with high interconnectivity in natural wood. Herein, by converting the honeycombed structure of natural wood into a lamellar architecture via structural engineering, we develop a flexible wood sponge with vertically aligned channels for efficient and salt-resistant solar desalination after surface coating with carbon nanotubes (CNTs). The special lamellar structure with an interlayer distance of 50-300 µm provides the wood sponge with faster water transport, lower thermal conductivity, and water evaporation enthalpy, thus achieving higher evaporation performances in comparison with the cellular structure of natural wood. Noteworthy, the vertically aligned channels of the wood sponge facilitate sufficient fluid convection and diffusion and enable efficient salt exchanges between the heating interface and the underlying bulk water, thus preventing salt accumulation on the surface. Benefiting from the distinctive lamellar structure, the developed wood-sponge evaporator exhibits exceptional salt resistance even in a hypersaline brine (20 wt %) during continuous 7-day desalination under 1 sun irradiation, with a high evaporation rate (1.38-1.43 kg m-2 h-1), outperforming most previously reported wood-based evaporators. The lamellar wood sponge may provide a promising strategy for desalinating high-salinity brines in an efficient manner.
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Introduction: Melanoma is a common and aggressive type of skin cancer with rising incidence rate globally. Gender is one of the determining factors, and overall males have a higher risk of developing melanoma as well as worse prognosis. Emerging evidence show that GPR68, a G protein-coupled receptor that is sensitive to acid and mechanical stimulations for cellular microenvironment, plays an important role in tumor biology. However, whether GPR68 is involved in gender-dependent regulation of tumor growth is unclear. Methods: We established a syngeneic melanoma model in Gpr68-deficient mice and investigated tumor growth in males and females. The GPR68 activation-induced cellular responses of melanocytes, including intracellular calcium dynamics, proliferation and migration were measured. The landscape of tumor-infiltrating immune cells were analyzed by flow cytometry and the expression various cytokines were checked by qRT-PCR. Results: GPR68 is required for melanoma growth in males but dispensable in females. GPR68 is expressed and functional in B16-F10 melanocytes, but the activity of the receptor does not directly contribute to proliferation and migration of the cells. GPR68 inhibits infiltration of CD45+ lymphocytes, CD8+ T cells and NK cells in melanoma in male mice, but has no apparent effect in females. Furthermore, GPR68 functionally inhibits the expression of IFNγ in the tumor infiltrating CD8+ T cells and NK cells as well as the inflammatory cytokine expression in the spleen in male mice but not in females. Our results show the gender-dependent modulatory effect of GPR68 on tumor-infiltrating immune cells and their tumor-killing capacity. Discussion: GPR68 is sensor for acid and mechanical stimulations, which are two important factors in the microenvironment associated with tumor growth and metastasis. Our results suggest a prominent role of the receptor molecules in tumor biology in a gender-dependent manner. Since GPCRs are more feasible to develop small molecule drugs compared to transcription factors, our study demonstrates the potential of GPR68 as a novel druggable therapeutic target for melanoma in male patients.
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Inflammatory bowel disease (IBD) is a chronic, non-specific, recurrent inflammatory disease, majorly affecting the gastrointestinal tract. Due to its unclear pathogenesis, the current therapeutic strategy for IBD is focused on symptoms alleviation. Autophagy is a lysosome-mediated catabolic process for maintaining cellular homeostasis. Genome-wide association studies and subsequent functional studies have highlighted the critical role of autophagy in IBD via a number of mechanisms, including modulating macrophage function. Macrophages are the gatekeepers of intestinal immune homeostasis, especially involved in regulating inflammation remission and tissue repair. Interestingly, many autophagic proteins and IBD-related genes have been revealed to regulate macrophage function, suggesting that macrophage autophagy is a potentially important process implicated in IBD regulation. Here, we have summarized current understanding of macrophage autophagy function in pathogen and apoptotic cell clearance, inflammation remission and tissue repair regulation in IBD, and discuss how this knowledge can be used as a strategy for IBD treatment.
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AIMS: To explore the association between low-density lipoprotein-cholesterol (LDL-C) and all-cause and cause-specific mortality based on a prospective cohort study. METHODS: Among 10850 individuals enrolled from National Health and Nutrition Examination Survey (NHANES) 1999-2014, 1355 (12.5%) died after an average follow-up of 5.7 years. Cox proportional regression models were used to determine the association between LDL-C with the risk of mortality. RESULTS: The level of LDL-C was L-shaped associated with the risk of all-cause mortality, namely a low level was related to an increased mortality risk. The level of LDL-C associated with the lowest risk of all-cause mortality was 124 mg/dL (3.2 mmol/L) in the overall population, and 134 mg/dL (3.4 mmol/L) in individuals not receiving lipid lowering treatment. Compared with participants with LDL-C of 110-134 mg/dL (2.8-3.5 mmol/L), the multivariable adjusted hazard ratio was 1.18 (95% confidence interval 1.01 to 1.38) for individuals with the lowest quartile for all-cause mortality. In participants with coronary heart diseases, the conclusion was similar but the critical point was lower. CONCLUSIONS: We found that low levels of LDL-C increased the risk of all-cause mortality, and the lowest risk of all-cause mortality for LDL-C concentration was 124 mg/dL (3.2 mmol/L). Our results provide a reasonable range of LDL-C when to initiate a statin therapy in clinical practice.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Cholesterol, LDL , Nutrition Surveys , Cause of Death , Prospective Studies , Risk , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Risk FactorsABSTRACT
Modeling cyber risks has been an important but challenging task in the domain of cyber security, which is mainly caused by the high dimensionality and heavy tails of risk patterns. Those obstacles have hindered the development of statistical modeling of the multivariate cyber risks. In this work, we propose a novel approach for modeling the multivariate cyber risks which relies on the deep learning and extreme value theory. The proposed model not only enjoys the high accurate point predictions via deep learning but also can provide the satisfactory high quantile predictions via extreme value theory. Both the simulation and empirical studies show that the proposed approach can model the multivariate cyber risks very well and provide satisfactory prediction performances.