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Merging two droplets into a droplet to add and mix two contents is one of the common droplet microfluidic functions with droplet generation and sorting, performing broad ranges of biological and chemical assays in droplets. However, traditional droplet-merging techniques often encounter unsynchronized droplets, causing overmerging or mis-merging, and unwanted merging outside of the desired zone. This is more severe when the incoming droplets to be merged are polydisperse in their sizes, often observed in assays that require long-term incubation, elevated-temperature, and/or multiple droplet processing steps. Here, we developed an interdigitated electrode (IDE)-based droplet merger consisting of a droplet autosynchronizing channel and a merging channel. The autosynchronizing channel provides >95% merging efficiency even when 20% polydispersity in the droplet size exists. The highly localized and enhanced dielectrophoretic force generated by the IDEs on the channel bottom allows droplet merging at an extremely low voltage (4.5 V) and only locally at the IDE region. A systematic evaluation of how various design and operation parameters of the IDE merger, such as IDE finger dimensions, dielectric coating layer thickness, droplet size, and droplet flow speed impact the performance was conducted. The optimized device showed consistent performance even when operating for up to 100 h consecutively at high throughput (100 droplets/s). The presented technology has been integrated into a droplet microfluidics workflow to test the lytic activities of bacteriophage on bacterial host cells with 100% merging efficiency. We expect this function to be integrated into droplet microfluidic systems performing broad ranges of high-throughput chemical and biological assays.
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BACKGROUND: The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4). RESULTS: There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis.
Subject(s)
Biomarkers , Blood Glucose , Non-alcoholic Fatty Liver Disease , Nutrition Surveys , Triglycerides , Humans , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/mortality , Non-alcoholic Fatty Liver Disease/diagnosis , Male , Female , Middle Aged , Triglycerides/blood , Risk Assessment , Blood Glucose/metabolism , Biomarkers/blood , Adult , Prognosis , Risk Factors , Time Factors , Aged , United States/epidemiology , Cause of Death , Predictive Value of Tests , Body Mass Index , Fatty Liver/mortality , Fatty Liver/blood , Fatty Liver/diagnosis , Waist CircumferenceABSTRACT
The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.
Subject(s)
Genetic Predisposition to Disease , Genotype , Hepatitis C , Polymorphism, Single Nucleotide , Humans , Male , Female , Case-Control Studies , Hepatitis C/genetics , Hepatitis C/virology , Hepatitis C/immunology , Middle Aged , Adult , HLA-A Antigens/genetics , Hepacivirus/genetics , Hepacivirus/immunology , Receptors, KIR/genetics , Aged , Receptors, KIR3DL2/geneticsABSTRACT
INTRODUCTION: Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner-Whitehouse 3 (TW-3) method. METHODS: Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts' mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident. RESULTS: For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed. CONCLUSION: In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy.
Assessing bone age, or how developed a child's skeleton is, is important in medical care, but the standard method can be time-consuming. Using AI to automatically assess bone age from X-ray images may improve efficiency without reducing accuracy. In this study, we evaluated how well an AI-powered X-ray bone age analyzer performed compared to the established TannerWhitehouse 3 (TW-3) method. X-ray images from 900 Chinese children and adolescents were collected from 30 centers. Six doctors (three experts, three residents) and the AI system independently assessed the TW-3 radius, ulna, and short bones (RUS) and TW-3 carpal bone age. The experts' assessments were considered the gold standard. The AI analyzer had an average error of 0.48 years for TW3-RUS bone age, with 87% of assessments within 1 year of the experts. For TW3 carpal bone age, the AI had an average error of 0.48 years, with 89% within 1 year. These results were similar to or better than those of the resident raters. These findings show the AI-powered analyzer can assess bone age as accurately as human raters. This technology may improve clinical efficiency by reducing the time required for bone age assessments without compromising accuracy.
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BACKGROUND: Glehnia littoralis is a medicinal and edible plant species having commercial value and has several hundred years of cultivation history. Polyploid breeding is one of the most important and fastest ways to generate novel varieties. To obtain tetraploids of G. littoralis in vitro, colchicine treatment was given to the seeds and then were screened based on morphology, flow cytometry, and root tip pressing assays. Furthermore, transcriptome analysis was performed to identity the differentially expressed genes associated with phenotypic changes in tetraploid G. littoralis. RESULTS: The results showed that 0.05% (w/v) colchicine treatment for 48 h was effective in inducing tetraploids in G. littoralis. The tetraploid G. littoralis (2n = 4x = 44) was superior in leaf area, leaf thickness, petiole diameter, SPAD value (Chl SPAD), stomatal size, epidermal tissues thickness, palisade tissues thickness, and spongy tissues thickness to the diploid ones, while the stomatal density of tetraploids was significantly lower. Transcriptome sequencing revealed, a total of 1336 differentially expressed genes (DEGs) between tetraploids and diploids. Chromosome doubling may lead to DNA content change and gene dosage effect, which directly affects changes in quantitative traits, with changes such as increased chlorophyll content, larger stomata and thicker tissue of leaves. Several up-regulated DEGs were found related to growth and development in tetraploid G. littoralis such as CKI, PPDK, hisD and MDP1. KEGG pathway enrichment analyses showed that most of DEGs were enriched in metabolic pathways. CONCLUSIONS: This is the first report of the successful induction of tetraploids in G. littoralis. The information presented in this study facilitate breeding programs and molecular breeding of G. littoralis varieties.
Subject(s)
Gene Expression Profiling , Phenotype , Tetraploidy , Transcriptome , Colchicine/pharmacology , Caryophyllales/genetics , Gene Expression Regulation, Plant , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Leaves/anatomy & histologyABSTRACT
Purpose: Negotiable fate as a belief in coping with the difficulties and uncertainties of life has an impact on people's mental health. This study aims to understand the influence of negotiate fate on college students' life satisfaction and its underlying mechanism. Methods: A cross-sectional study was conducted with the participation of 1523 students from six universities across China. The study aimed to measure the variables of negotiable fate, self-esteem, positive psychological capital, and life satisfaction of all participants. To investigate the effect of negotiable fate on college students' life satisfaction and the mediating roles of self-esteem and positive psychological capital in this relationship, a serial mediation effects model using Hayes' PROCESS was employed. Results: The results suggest that negotiable fate has a positive predictive effect on college students' life satisfaction. The impact of negotiable fate on college students' life satisfaction was mediated by self-esteem and positive psychological capital, and the chained mediation of self-esteem and positive psychological capital. Conclusion: To summarize, the belief of negotiable fate has practical significance for the enhancement of college student's mental health and quality of life, and the cultivation of college students' belief of negotiable fate can be actively promoted in the future to help them better cope with the uncertainties and challenges in their lives to improve their life satisfaction.
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Carbon-based nanomaterials (CBNM)have been widely used in various fields due to their excellent physicochemical properties. In particular, in the area of tumor diagnosis and treatment, researchers have frequently reported them for their potential fluorescence, photoacoustic (PA), and ultrasound imaging performance, as well as their photothermal, photodynamic, sonodynamic, and other therapeutic properties. As the functions of CBNM are increasingly developed, their excellent imaging properties and superior tumor treatment effects make them extremely promising theranostic agents. This review aims to integrate the considered and researched information in a specific field of this research topic and systematically present, summarize, and comment on the efforts made by authoritative scholars. In this review, we summarized the work exploring carbon-based materials in the field of tumor imaging and therapy, focusing on PA imaging-guided photothermal therapy (PTT) and discussing their imaging and therapeutic mechanisms and developments. Finally, the current challenges and potential opportunities of carbon-based materials for PA imaging-guided PTT are presented, and issues that researchers should be aware of when studying CBNM are provided.
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As the leading killer of life and health, stroke leads to limb paralysis, speech disorder, dysphagia, cognitive impairment, mental depression and other symptoms, which entail a significant financial burden to society and families. At present, physiology, clinical medicine, engineering, and materials science, advanced biomaterials standing on the foothold of these interdisciplinary disciplines provide new opportunities and possibilities for the cure of stroke. Among them, hydrogels have been endowed with more possibilities. It is well-known that hydrogels can be employed as potential biosensors, medication delivery vectors, and cell transporters or matrices in tissue engineering in tissue engineering, and outperform many traditional therapeutic drugs, surgery, and materials. Therefore, hydrogels become a popular scaffolding treatment option for stroke. Diverse synthetic hydrogels were designed according to different pathophysiological mechanisms from the recently reported literature will be thoroughly explored. The biological uses of several types of hydrogels will be highlighted, including pro-angiogenesis, pro-neurogenesis, anti-oxidation, anti-inflammation and anti-apoptosis. Finally, considerations and challenges of using hydrogels in the treatment of stroke are summarized.
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Biosensing Techniques , Stroke , Humans , Hydrogels/therapeutic use , Biocompatible Materials , Tissue Engineering , Stroke/drug therapyABSTRACT
Background: Inherited phenylalanine hydroxylase deficiency, also known as phenylketonuria (PKU), causes poor growth and neurologic deficits in the untreated state. After ascertainment through newborn screen and dietary phenylalanine (Phe) restriction to achieve plasma Phe in the range of 120-360 µmol/L, these disease manifestations can be prevented. Poor compliance with protein restricted diets supported by medical food is typical in later years, beginning in the late toddler and teenage years. Pharmacologic doses of oral tetrahydrobiopterin (BH4; sapropterin dihydrochloride) is effective in reducing plasma Phe in about 40-50% of PKU patients but effectiveness is highly variable. Objective: To assess the maximal responsiveness to 20 mg/kg/day oral BH4 as it affects plasma Phe and dietary Phe allowance in PKU patients. Materials and methods: This was a single-center, retrospective observational study, combining case reports of individual patients. We reported an outcome of 85 patients with PKU who were trialed on BH4. Phe levels and dietary records of 19 BH4 "super-responders" were analyzed. Results: Overall, 63.5% of the patients (54/85) were considered BH4 responders. However, we quantitated the dietary liberalization of 19 of our responsive patients (35%), those with at least a 2-fold increase in dietary Phe and maintenance of plasma Phe in treatment range. In these "super-responders", the mean plasma Phe at baseline was 371 ± 237 µmol/L and decreased to 284 ± 273 µmol/L after 1 year on BH4. Mean dietary Phe tolerance increased significantly from 595 ± 256 to 2260 ± 1414 mg/day (p ≤0.0001), while maintaining mean plasma Phe levels within treatment range. Four patients no longer required dietary Phe restriction and could discontinue medical food. The majority of patients had at least one BH4-responsive genotype. Conclusion: This cohort demonstrates the maximally achievable dietary liberalization which some PKU patients may expect with BH4 therapy. Health benefits are considered to accrue in patients with increased intact protein.
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This study explored the potential of purple potato anthocyanins (PPAs) in regulating the digestive properties of starches of various crystalline types. In vitro digestion experiments indicated that PPAs inhibit the hydrolysis of rice starch (A-type) better than that of garden pea starch (C-type) and potato starch (B-type). Further structural assessment of different PPA-starch systems showed that PPAs and starch likely interact through non-covalent bonds, resulting in structural changes. Microstructural changes observed in the starches were consistent with the in vitro digestion results, and the chain length and proportions of short/long chains in amylopectin molecules affected the binding strengths and interaction modes between PPAs and starch. Hence, the three starches differed in their PPA loading efficiency and digestibility. These discoveries contribute to a deeper understanding of the mechanisms underlying the inhibition of starch digestibility by PPAs. They can aid the formulation of value-added products and low-glycemic-index foods.
Subject(s)
Anthocyanins , Solanum tuberosum , Solanum tuberosum/chemistry , Digestion , Starch/chemistry , Amylopectin/chemistryABSTRACT
Early detection of acute kidney injury (AKI) may provide a crucial window of opportunity to prevent further injury, which helps improve clinical outcomes. This study aimed to develop a deep interpretable network for continuously predicting the 24-hour AKI risk in real-time and evaluate its performance internally and externally in critically ill patients. A total of 21,163 patients' electronic health records sourced from Beth Israel Deaconess Medical Center (BIDMC) were first included in building the model. Two external validation populations included 3025 patients from the Philips eICU Research Institute and 2625 patients from Zhongda Hospital Southeast University. A total of 152 intelligently engineered predictors were extracted on an hourly basis. The prediction model referred to as DeepAKI was designed with the basic framework of squeeze-and-excitation networks with dilated causal convolution embedded. The integrated gradients method was utilized to explain the prediction model. When performed on the internal validation set (3175 [15 %] patients from BIDMC) and the two external validation sets, DeepAKI obtained the area under the curve of 0.799 (95 % CI 0.791-0.806), 0.763 (95 % CI 0.755-0.771) and 0.676 (95 % CI 0.668-0.684) for continuousAKI prediction, respectively. For model interpretability, clinically relevant important variables contributing to the model prediction were informed, and individual explanations along the timeline were explored to show how AKI risk arose. The potential threats to generalisability in deep learning-based models when deployed across health systems in real-world settings were analyzed.
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Acute Kidney Injury , Critical Illness , Humans , Risk Assessment , Risk Factors , Patients , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiologyABSTRACT
BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) is a newly developed strategy for treating acute liver failure (ALF). Nonetheless, the low survival rate of MSCs after transplantation and their poor homing to damaged tissues limit the clinical application of MSCs. The research assessed whether hypoxic preconditioning (HPC) can improve the biological activity of human amniotic mesenchymal stem cells (hA-MSCs), promote their homing ability to the liver of mice with ALF, and influence liver tissue repair. METHODS: Flow cytometry, CCK8, Transwell, and Western blotting assays were conducted to assess the effects of hypoxic preconditioning on the phenotype, proliferation, and migration of hA-MSCs and the changes in the c-Met and CXCR4 gene expression levels were studied. To evaluate the effects of the transplantation of hypoxic preconditioning of hA-MSCs on the homing and repair of D-galactosamine (D-GalN)/LPS-induced ALF, the mechanism was elucidated by adding c-Met, CXCR4-specific blockers (SU11274 and AMD3100). RESULTS: After hypoxia pretreatment (1% oxygen volume fraction), hA-MSCs maintained the morphological characteristics of adherence and vortex colony growth and showed high CD44, CD90, and CD105 and low CD31, CD34, and CD45 expression levels. Hypoxic preconditioning of hA-MSCs significantly increased their proliferation and migration and highly expressed the c-Met and CXCR4 genes. In vivo and in vitro, this migration-promoting effect was suppressed by the c-Met specific blocker SU11274. In the acute liver failure mouse model, the HGF expression level was considerably elevated in the liver than that in the serum, lungs and kidneys. The transplantation of hypoxic preconditioned hA-MSCs introduced a remarkable improvement in the liver function and survival rate of mice with ALF and enhanced the anti-apoptosis ability of liver cells. The anti-apoptotic enhancing effect of hypoxic preconditioning was suppressed by the c-Met specific blocker SU11274. Hypoxic hA-MSCs administration was observed to have considerably increased the fluorescent cells in the liver than that recorded after administering normal oxygen-hA-MSCs. The number of hepatic fluorescent cells decreased remarkably after adding the c-Met inhibitor SU11274, compared to that recorded after hypoxic pretreatment, whereas the effect of c-Met inhibitor SU11274 on normal oxygen-hA-MSCs was not significant. CONCLUSIONS: Hypoxic preconditioning depicted no impact on the morphology and phenotype features of the human amniotic mesenchymal stem cells, but it can promote their proliferation, migration, anti-apoptotic effect, and homing rate and improve the repair of acute liver failure, which might be mediated by the HGF/c-Met signaling axis.
Subject(s)
Indoles , Liver Failure, Acute , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Piperazines , Sulfonamides , Humans , Mice , Animals , Liver Failure, Acute/therapy , Liver Failure, Acute/metabolism , Hypoxia/metabolism , Oxygen/metabolism , Cell Proliferation , Hepatocyte Growth Factor/metabolism , Hepatocyte Growth Factor/pharmacologyABSTRACT
Developing cost-efficient trifunctional catalysts capable of facilitating hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR) activity is essential for the progression of energy devices. Engineering these catalysts to optimize their active sites and integrate them into a cohesive system presents a significant challenge. This study introduces a nanoflower (NFs)-like carbon-encapsulated FeNiPt nanoalloy catalyst (FeNiPt@C NFs), synthesized by substituting Co2+ ions with high-spin Fe2+ ions in Hofmann-type metal-organic framework, followed by carbonization and pickling processes. The FeNiPt@C NFs catalyst, characterized by its nitrogen-doped carbon-encapsulated metal alloy structure and phase-segregated FeNiPt alloy with slight surface oxidization, exhibits excellent trifunctional catalytic performance. This is evidenced by its activities in HER (-25 mV at 10 mA cm-2), ORR (half-wave potential of 0.93 V), and OER (294 mV at 10 mA cm-2), with the enhanced water oxidation activity attributed to the high-spin state of the Fe element. Consequently, the Zn-air battery and anion exchange membrane water electrolyzer assembled by FeNiPt@C NFs catalyst demonstrate remarkable power density (168 mW cm-2) and industrial-scale current density (698 mA cm-2 at 1.85 V), respectively. This innovative integration of multifunctional catalytic sites paves the way for the advancement of sustainable energy systems.
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A significant hurdle for the widespread implementation and use of synthetic biology is the challenge of highly efficient introduction of DNA into microorganisms. This is especially a barrier for the utilization of non-model organisms and/or novel chassis species for a variety of applications, ranging from molecular biology to biotechnology and biomanufacturing applications. Common approaches to episomal and chromosomal gene editing, which employ techniques such as chemical competence and electroporation, are typically only amenable to a small subset of microbial species while leaving the vast majority of microorganisms in nature genetically inaccessible. To address this challenge, we have employed the previously described B. subtilis broad-host conjugation strain, XPORT, which was modularly designed for loading DNA cargo and conjugating such DNA into recalcitrant microbes. In this current work, we have leveraged and adapted the XPORT strain for use in a droplet microfluidic platform to enable increased efficiency of conjugation-based DNA transfer. The system named DNA ENTRAP (DNA ENhanced TRAnsfer Platform) utilizes cell-encapsulated water-in-oil emulsion droplets as pico-liter-volume bioreactors that allows controlled contacts between the donor and receiver cells within the emulsion bioreactor. This allowed enhanced XPORT-mediated genetic transfer over the current benchtop XPORT process, demonstrated using two different Bacillus subtilis strains (donor and receiver), as well as increased throughput (e.g., number of successfully conjugated cells) due to the automated assay steps inherent to microfluidic lab-on-a-chip systems. DNA ENTRAP paves the way for a streamlined automation of culturing and XPORT-mediated genetic transfer processes as well as future high-throughput cell engineering and screening applications.
Subject(s)
DNA , Microfluidics , Microfluidics/methods , Emulsions , DNA/genetics , Biotechnology , PlasmidsABSTRACT
BACKGROUND: Frequent hand washing and disinfection during the corona virus disease (COVID-19) pandemic may lead to skin-related disability. The causal relationship between atopic dermatitis (AD), the most common chronic, noninfectious, inflammatory skin disease, and COVID-19 remains unclear. We used Mendelian randomization (MR) to explore the causal inference of atopic dermatitis with COVID-19 outcomes. METHODS: Genome-wide association study (GWAS) data for AD, consisting of 8383 cases and 236,162 controls of European ethnicity, were provided by the FinnGen database. The GWAS outcome data were derived from the COVID-19 Host Genetics Initiative and consisted of COVID-19 susceptibility (122,616 cases and 2,475,240 controls), hospitalization (32,519 cases and 2,062,805 controls), and very severe respiratory disease (13,769 cases and 1,072,442 controls). The inverse variance weighted with a fixed effects model (IVW (fe)) was used as the main statistical approach to assess the causality between AD and COVID-19 in this study. Several other analytical methods have also been used to complement or identify pleiotropy and heterogeneity. RESULTS: MR analysis showed no causality between AD and COVID-19 outcomes. The odds ratios (OR) were 1.00 (95% confidence interval (CI), 0.99-1.02) for susceptibility, 1.00 (95% CI, 0.96-1.04) for hospitalization, 0.97 (95% CI, 0.92-1.03) for very severe respiratory disease by the method of IVW (fe). CONCLUSION: In conclusion, we found no causal relationship between AD and COVID-19 outcomes. This study provides additional ideas for the exploration of the risk factors for COVID-19.
Subject(s)
COVID-19 , Dermatitis, Atopic , Virus Diseases , Humans , Dermatitis, Atopic/epidemiology , Dermatitis, Atopic/genetics , Genome-Wide Association Study , Mendelian Randomization AnalysisABSTRACT
Noisy labels are often encountered in datasets, but learning with them is challenging. Although natural discrepancies between clean and mislabeled samples in a noisy category exist, most techniques in this field still gather them indiscriminately, which leads to their performances being partially robust. In this paper, we reveal both empirically and theoretically that the learning robustness can be improved by assuming deep features with the same labels follow a student distribution, resulting in a more intuitive method called student loss. By embedding the student distribution and exploiting the sharpness of its curve, our method is naturally data-selective and can offer extra strength to resist mislabeled samples. This ability makes clean samples aggregate tightly in the center, while mislabeled samples scatter, even if they share the same label. Additionally, we employ the metric learning strategy and develop a large-margin student (LT) loss for better capability. It should be noted that our approach is the first work that adopts the prior probability assumption in feature representation to decrease the contributions of mislabeled samples. This strategy can enhance various losses to join the student loss family, even if they have been robust losses. Experiments demonstrate that our approach is more effective in inaccurate supervision. Enhanced LT losses significantly outperform various state-of-the-art methods in most cases. Even huge improvements of over 50% can be obtained under some conditions.
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The engineering of amorphous metal-organic frameworks (MOFs) offers potential opportunities for the construction of electrocatalysts for efficient oxygen evolution reaction (OER). Herein, highly efficient OER performance and durability in alkaline electrolyte are discovered for MOF-derived amorphous and porous electrocatalysts, which are synthesized in a brief procedure and can be facilely produced in scalable quantities. The structural inheritance of MOF amorphous catalysts is significant for the retention of catalytic sites and the diffusion of electrolytes, and the presence of Fe sites can change the electronic structure and effectively control the adsorption behavior of important intermediates, accelerating reaction kinetics. The obtained amorphous A-FeNi can be transformed from FeNi-MOF effortlessly and instantly, and it only needs low overpotentials of 152 and 232 mV at 10 and 100 mA cm-2 with a Tafel slope of 17 mV dec-1 in 1 m KOH for OER. Moreover, A-FeNi possesses high corrosion resistance and durability, therefore A-FeNi can work continually for at least 400 h at 100 mA cm-2. This work may pave a new avenue for the design of MOFs-related amorphous electrocatalyst.
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BACKGROUND: The H5N1 influenza virus is a cause of severe pneumonia. Co-infection of influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to poor prognosis of patients during the COVID-19 epidemic. However, reports on patients co-infected with avian influenza virus and SARS-CoV-2 are scarce. CASE PRESENTATION: A 52-year-old woman presented with a fever, which has persisted for the past eight days, along with worsening shortness of breath and decreased blood pressure. Computed tomography (CT) revealed an air bronchogram, lung consolidation, and bilateral pleural effusion. The subsequent polymerase chain reaction (PCR) of the bronchoalveolar lavage fluid (BALF) revealed positivity for H5N1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSION: The H5N1 influenza virus is a cause of severe pneumonia. The clinical presentation of the patient had a predomination of H5N1 influenza rather than COVID-19. A PCR analysis for the identification of the virus is necessary to reveal the pathogen causing the severe pneumonia. The patient exhibited an excellent prognosis upon the use of the appropriate antiviral medicine.
Subject(s)
COVID-19 , Coinfection , Influenza A Virus, H5N1 Subtype , Pneumonia , Female , Humans , Middle Aged , SARS-CoV-2 , COVID-19/diagnosis , Coinfection/diagnosisABSTRACT
Gancao Xiexin Decoction (GCXXD) is a traditional Chinese decoction that is often used in treating gastric ulcers. However, the substance basis and mechanism of action remain unclear. In this study, in vivo and in vitro components of GCXXD were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry. The compound Discover platform was used to ultimately enable rapid identification of compounds. Acquire X intelligent data acquisition technology software was innovatively adopted. In the process of collecting drug-containing plasma, all components detected in blank plasma samples were excluded to eliminate the interference and influence of endogenous components in plasma, making the analysis results more accurate and reliable. At the same time, the possibility of selecting precursor parent ions with low concentration levels within the chromatographic peak can be increased, improving the coverage and integrality of the detection of components in vivo. Also, the targeted network pharmacology strategy combined with molecular docking was established to explore the mechanism of GCXXD in treating gastric ulcers. As a result, 113 components were identified, 41 of which could enter the bloodstream and exert therapeutic effects in vivo. The main effective components are glycyrrhizic acid, 6-gingerol, jatrorrhizine, wogonin, palmatine, and liquiritigenin, main targets in vivo were related to ALB, IL6, and VEGF, which play an important role in anti-inflammatory and promoting angiogenesis. In summary, this study adopted a comprehensive analysis strategy to reveal the pharmacodynamic material basis and mechanism of GCXXD against gastric ulcers, providing a scientific basis for its clinical application.