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Pathway analysis, including nontopology-based (non-TB) and topology-based (TB) methods, is widely used to interpret the biological phenomena underlying differences in expression data between two phenotypes. By considering dependencies and interactions between genes, TB methods usually perform better than non-TB methods in identifying pathways that include closely relevant or directly causative genes for a given phenotype. However, most TB methods may be limited by incomplete pathway data used as the reference network or by difficulties in selecting appropriate reference networks for different research topics. Here, we propose a gene set correlation enrichment analysis method, Gscore, based on an expression dataset-derived coexpression network to examine whether a differentially expressed gene (DEG) list (or each of its DEGs) is associated with a known gene set. Gscore is better able to identify target pathways in 89 human disease expression datasets than eight other state-of-the-art methods and offers insight into how disease-wide and pathway-wide associations reflect clinical outcomes. When applied to RNA-seq data from COVID-19-related cells and patient samples, Gscore provided a means for studying how DEGs are implicated in COVID-19-related pathways. In summary, Gscore offers a powerful analytical approach for annotating individual DEGs, DEG lists, and genome-wide expression profiles based on existing biological knowledge.
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COVID-19 , Transcriptoma , Humanos , Transcriptoma/genética , Perfilação da Expressão Gênica/métodos , Fenótipo , COVID-19/genética , Redes Reguladoras de Genes/genéticaRESUMO
OBJECTIVE: This study aims to translate the Pectus Excavatum Evaluation Questionnaire(PEEQ) into Chinese, and to comprehensively assess subjective outcomes in quality of life of children with pectus excavatum. METHODS: The PEEQ was translated from English to Chinese as according to the PRO translation guidelines. Structural validity and reliability of the questionnaire were examined by validated factor analysis and Cronbach's alpha coefficient analysis respectively. RESULTS: The results of the validation factor analysis for the Chinese PEEQ parent's and child's questionnaires demonstrated that the fit indicators for each dimension met the required criteria. The overall Cronbach's alpha coefficient of parent's and child's questionnaires were 0.840 and 0.854. Both the item-level content validity index (I-CVI) and scale-level content validity index (S-CVI) of each sub-questionnaire were 1. CONCLUSION: The Chinese version of the PEEQ parent's questionnaire is suitable as a proxy assessment for patients with PE, but the child's questionnaire needs further adjustments.
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Tórax em Funil , Qualidade de Vida , Criança , Humanos , Povo Asiático , China , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Rich biological information in sweat provides great potential for health monitoring and management. However, due to the complexity of sweat, the development of environmentally friendly green electronic products is of great significance to the construction of ecological civilization. This study utilized a simple combination of polystyrene sulfonate sodium (PSS) and filter paper (FP) to prepare cellulose materials coated with conductive polymers, developing an electrochemical sensor based on the modified materials. The mechanical and electrochemical properties of the fabricated PSS/FP membrane were optimized by adjusting the feeding dosage of PSS. The realized PSS/FP composite containing 7% PSS displayed good conductivity (9.1 × 10-2 S/m), reducing electric resistance by 99.2% compared with the original FP membrane (6.7 × 10-4 S/m). The stable current of the membrane in simulated sweat under different pH environments is highly correlated with the pH values. Additionally, when the membrane is exposed to simulated sweat with varying ion concentrations, the current signal changes in real time with the concentration variations. The response time averages around 0.3 s.
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Celulose , Condutividade Elétrica , Poliestirenos , Suor , Suor/química , Celulose/química , Concentração de Íons de Hidrogênio , Poliestirenos/química , Polímeros/química , Humanos , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodosRESUMO
Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.
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Biônica , Restauração Dentária Permanente , Doenças da Boca , HumanosRESUMO
Misinformation has posed significant threats to all aspects of people's lives. One of the most active areas of research in misinformation examines how individuals are misinformed. In this paper, we study how and to what extent agents are misinformed in an extended bounded confidence model, which consists of three parts: (i) online selective neighbors whose opinions differ from their own but not by more than a certain confidence level; (ii) offline neighbors, in a Watts-Strogatz small-world network, whom an agent has to communicate with even though their opinions are far different from their own; and (iii) a Bayesian analysis. Furthermore, we introduce two types of epistemically irresponsible agents: agents who hide their honest opinions and focus on disseminating misinformation and agents who ignore the messages received and follow the crowd mindlessly. Simulations show that, in an environment with only online selective neighbors, the misinforming is more successful with broader confidence intervals. Having offline neighbors contributes to being cautious of misinformation, while employing a Bayesian analysis helps in discovering the truth. Moreover, the agents who are only willing to listen to the majority, regardless of the truth, unwittingly help to bring about the success of misinformation attempts, and they themselves are, of course, misled to a greater extent.
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Sulfation widely exists in the eukaryotic proteome. However, understanding the biological functions of sulfation in peptides and proteins has been hampered by the lack of methods to control its spatial or temporal distribution in the proteome. Herein, we report that fluorosulfate can serve as a latent precursor of sulfate in peptides and proteins, which can be efficiently converted to sulfate by hydroxamic acid reagents under physiologically relevant conditions. Photocaging the hydroxamic acid reagents further allowed for the light-controlled activation of functional sulfopeptides. This work provides a valuable tool for probing the functional roles of sulfation in peptides and proteins.
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Proteoma , Sulfatos , Peptídeos , Eucariotos , Ácidos Hidroxâmicos , Óxidos de EnxofreRESUMO
In order to prevent drugs from being captured and degraded by the acidic environment of organelles, such as lysosomes, after entering cells, this study designed and synthesized a novel carrier amphiphilic polypeptide (DGRHHHLLLAAAA), designated P13, for use as a tumor-targeting drug delivery vehicle. The P13 peptide was synthesized by the solid phase synthesis method, and its self-assembly behavior and drug-loading capacity in aqueous solution were studied and characterizedin vitro. Doxorubicin (DOX) was loaded by dialysis method, and P13 and DOX were mixed at a mass ratio of 6:1 to form regular rounded globules. The acid-base buffering capacity of P13 was investigated determined by acid-base titration. The results revealed that P13 had excellent acid-base buffering capacity, a critical micelle concentration value of about 0.000 21 g l-1, and the particle size of P13-Dox nanospheres was 167 nm. The drug encapsulation efficiency and drug loading capacity of micelles were 20.40 ± 1.21% and 21.25 ± 2.79%, respectively. At the concentration of 50µg ml-1of P13-DOX , the inhibition rate was 73.35%. The results of thein vivoantitumor activity assay in mice showed that P13-DOX also exhibited excellent inhibitory effect on tumor growth, compared with the tumor weight of 1.1 g in the control group, the tumor weight in the P13-DOX-treated group was only 0.26 g. Additionally, the results of hematoxylin and eosin staining of the organs showed that P13-DOX had no damaging effect on normal tissues. The novel amphiphilic peptide P13 with proton sponge effect designed and prepared in this study is expected to be a promising tumor-targeting drug carrier with excellent application potential.
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Neoplasias , Prótons , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Micelas , Peptídeos/farmacologia , Neoplasias/tratamento farmacológico , Linhagem Celular TumoralRESUMO
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of LDLR, has emerged as an important target for the treatment of hypercholesterolemic cardiovascular disease, and monoclonal antibodies alirocumab and evolocumab against it have been widely used in clinical practice. The vaccine research of PCSK9 is considered a promising option for the long-term treatment and prevention of cardiovascular disease, but progress has been slow. The selection of safe and effective epitopes is one of the key steps in vaccine development. In this study, we designed a phage display library of cascaded peptides for affinity screening with two antibody drugs, and found that the two peptides PC3 and PS6, which are adjacent to each other in protein spatial structure, both have superior binding activity to the screening antibodies. We performed in vitro recombination design on the dominant sequences, and obtained recombinant sequences that can respond to the dominant conformational epitope of PCSK9, which provides a meaningful reference for epitope selection in subsequent PCSK9 vaccine development.
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Doenças Cardiovasculares , Epitopos , Pró-Proteína Convertase 9 , LDL-Colesterol , Epitopos/química , Humanos , Pró-Proteína Convertase 9/químicaRESUMO
Vortex beams carrying orbital angular momentum (OAM) have been widely applied in optical manipulations, optical micromachining, and high-capacity optical communications. Vortex mode detection is very important in various applications. However, the detection of near-infrared vortex modes is still difficult because of the wavelength limitations of the detection device. Here, we present a study on measuring optical near-infrared vortex modes with frequency upconversion, which can convert a near-infrared beam into a visible beam. In our experiment, the optical near-infrared vortex modes can be measured by the number and orientation of the fringes of the second harmonic intensity patterns. The proposed method is a convenient and flexible way to measure the different OAM of vortex beams, which may have potential applications in all kinds of circumstances that vortex modes involve.
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INTRODUCTION: Zoledronic acid (ZA) is a widely used bisphosphonate compound for the prevention of skeletal metastasis-associated osteolysis and treatment of post-menopause osteoporosis. Acute kidney injury is one of the commonly described renal complications. Electrolytes disorder has also been reported relevant to ZA exposure and nephrotoxicity. Syndrome of persistent hypophosphatemia, hypokalemia and metabolic acidosis is regarded as the initial signs of acute kidney injury. CASE PRESENTATION: We reported a 64-year-old female with bone metastasis from lung adenocarcinoma who received a 5-year history of 4-week cycle ZA infusion. She initially presented symptomatic severe hypophosphatemia and was finally identified with ZA-induced generalized tubular dysfunction as Fanconi's syndrome and distal renal tubular acidosis. Renal pathological findings revealed toxic renal tubular necrosis. The ZA infusion was thus extended to an 8-week cycle with oral phosphate supplementation and alfacalcidol. Although periodic changes pre- and post-ZA infusion existed yet, hypophosphatemia was effectively improved and the rapid decline of eGFR was partially delayed. We reviewed the literature and mainly summarized the characteristics of bisphosphonates-associated hypophosphatemia. Moderate hypophosphatemia was more frequently mentioned in contrast to severe cases being predisposed to be reported. And progressive hypophosphatemia serves as an early sign of kidney injury. CONCLUSION: Progressive electrolyte disorders and CKD were the long-term renal outcome of the current patient. We would like to arouse more attention to electrolytes imbalance related to early ZA-induced kidney injury and emphasize the significance of close monitoring.
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Angiogenesis plays a pivotal role in the recovery of neurological function after ischemia stroke. Herein, we investigated the effect of trilobatin (TLB) on angiogenesis after cerebral ischemia-reperfusion injury (CIRI). The effect of TLB on angiogenesis after CIRI were investigated in mouse brain microvascular endothelium bEnd.3 cells and middle cerebral artery occlusion (MCAO)-induced CIRI rat model. The cell proliferation and angiogenesis were observed using immunofluorescence staining. The cell cycle, expressions of cell cycle-related proteins and SIRT 1-7 were determined by flow cytometry and western blot, respectively. The binding affinity of TLB with SIRT7 was predicted by molecular docking. The results showed that TLB concentration-dependently promoted bEnd.3 cell proportion in the S-phase. TLB significantly increased the protein expressions of SIRT6, SIRT7, and VEGFA, but not affected SIRT1-SIRT5 protein expressions. Moreover, TLB not only dramatically alleviated neurological impairment after CIRI, but also enhanced post-stroke neovascularization and newly formed functional vessels in cerebral ischemic penumbra. Furthermore, TLB up-regulated the protein expressions of CDK4, cyclin D1, VEGFA and its receptor VEGFR-2. Intriguingly, TLB not only directly bound to SIRT7, but also increased SIRT7 expression at day 28. Our findings reveal that TLB promotes cerebral microvascular endothelial cells proliferation, and facilitates angiogenesis after CIRI via mediating SIRT7/VEGFA signaling pathway in rats. Therefore, TLB might be a novel restorative agent to rescue ischemia stroke.
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Flavonoides , Polifenóis , Traumatismo por Reperfusão , Sirtuínas , Animais , Células Endoteliais/metabolismo , Flavonoides/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Neovascularização Patológica , Polifenóis/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais , Sirtuínas/metabolismo , Fator A de Crescimento do Endotélio VascularRESUMO
Juice, as a liquid foodstuff, is subject to spoilage and damage due to complications during transport and storage. The appearance of intact outer packaging often makes spoilage and damage difficult to detect. Therefore, it of particular importance to develop a fast, real-time material to evaluate liquid foodstuffs. In this paper, starch films with pH response characteristics are successfully prepared by inorganic ion modification by utilizing whole starch and amylopectin as raw materials. The mechanical properties, stability properties, hydrophilic properties and pH electrical signal response indices of the films are analyzed and measured. The films exhibit good electrical conductivity values with 1.0 mL of ion addition (10 mmol/L), causing the composite film to respond sensitively to solutions with varying pH values. In the test of spoiled orange juice, the full-component corn starch (CS) film has more sensitive resistance and current responses, which is more conducive for applications in the quality monitoring of juice. The results indicate that modified starch films can potentially be applied in the real-time monitoring of the safety of liquid foodstuffs.
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Sucos de Frutas e Vegetais , Amido , Amido/química , Amilopectina , Embalagem de Alimentos/métodos , AlimentosRESUMO
PURPOSE: The scanning of plaster models for three-dimensional (3D) construction requires their rigid fixation in the intercuspal position. Factors such as installation, motion, and scanning procedures influenced the accuracy of this method, which ultimately influence the results. Therefore, the present study attempted to provide an optimal and accurate method with less complex procedures and a more accessible equipment for determining the intercuspal relation in the 3D occlusal construction of dental models. METHODS: A pair of plastic mounting plates that could be directly attached to a mechanical articulator was designed and 3D printed. Nine axial hemispherical concaves were introduced on the axial surface of each plate. The rigidly fixed maxillary and mandibular dental models were scanned directly. The distances DR between nine pairs of concaves on both mounting plates adhered to the maxillary and mandibular sections of the articulator were measured using the three-coordinate measuring machine Faro Edge as the reference. The present study comprised seven test groups varying in number and location. Assessing the reference points from each of the seven groups performed the 3D construction. The Geomagic Studio software was used to construct the concaves of digital casts, and the distances DM between the pairs of concaves were measured as test values. Variable differences between DR and DM were analyzed. RESULTS: An optimum distribution scheme was obtained for reference point registration by quantitatively evaluating accuracy levels of the 3D constructions of different reference point distribution patterns. This scheme can serve as a reference for related studies and dental clinic operations. CONCLUSIONS: Three-dimensional construction of the intercuspal relation during scanning of the maxillary and mandibular models with an accuracy of 0.046 mm ± 0.009 mm can be achieved using the improved design of mounting plates.
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Imageamento Tridimensional , Modelos Dentários , Articuladores Dentários , Humanos , Mandíbula , SoftwareRESUMO
Nervous necrosis virus (NNV) causes viral nervous necrosis (VNN), a disease that leads to almost 100% mortality among larvae and juvenile fish, severely affecting the aquaculture industry. VNN vaccines based on inactivated viruses or virus-like particles (VLPs) are unsuitable for fish fry with immature adaptive immune systems. Here, we applied an anti-NNV strategy based on affinity peptides (AFPs). Three phage display peptide libraries were screened against RBS, the VLP of orange-spotted grouper nervous necrosis virus (OGNNV). From the positive clones, a dodecapeptide with the highest binding capacity (BC) to RBS was selected. This AFP agglutinated or disrupted virion particles, inhibiting RBS entry into sea bass (SB) cells. To enhance BC and solubility, we amended the AFP sequence as "LHWDFQSWVPLL" and named as 12C. One to three copies of 12C in tandem were prokaryotically expressed with a maltose binding protein (MBP) linked by a flexible peptide. Of the recombinant proteins expressed, MBP-triple-12C (MBP-T12C) exhibited the highest BC, efficiently blocked RBS entry, and strongly inhibited OGNNV infection at viral entry. Moreover, MBP-T12C bound the VLPs of all NNV serotypes, displaying broad-spectrum anti-NNV ability, and recognized only OGNNV and mud crab virus, demonstrating binding specificity. Therefore, these anti-NNV AFPs specifically bound NNV, aggregating or disrupting the viral particles, to reduce the contact probability between the virus and cell surface, subsequently inhibiting viral infection. Our results not only provided a candidate of anti-NNV AFP, but a framework for the development of antiviral AFP.
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Bass , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Nodaviridae/fisiologia , Peptídeos/imunologia , Infecções por Vírus de RNA/veterinária , Internalização do Vírus , Animais , Antivirais/imunologia , Doenças dos Peixes/virologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/virologia , Proteínas Recombinantes/imunologiaRESUMO
The aims of this study were to observe the effects of vacuum sealing drainage (VSD) with three different negative pressures on the wound healing rate, macrophage count and the expression of hyaluronic acid (HA) as well as its receptor CD44 in seawater-immersed blast-injury wounds (SIBIW) and to determine the optimal negative pressure value. In a minipig SIBIW model, different suction pressures and routine dressing were applied. Histological and immunohistochemical comparisons as well as molecular biology methods were performed to compare the wound healing conditions, macrophage count and the levels of HA and CD44. The wound healing rate of the VSD group was significantly higher than that of the control group, with the -120 mmHg group exhibiting the best effects. The macrophage count of the VSD group was higher than that of the control group. The HA level fluctuation was higher in the VSD group, with the -120 mmHg and the -180 mmHg groups showing the most significant fluctuation (P < 0·05). CD44 was expressed in the full-thickness wound-limbic tissues and was higher in the treatment group than that in the control group, with the -120 mmHg group having the most obvious expression. VSD significantly improved the healing ability and increased the macrophage count and the HA content. It also promoted CD44 expression. -120 mmHg is the optimal negative pressure value.
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Traumatismos por Explosões , Drenagem , Humanos , Tratamento de Ferimentos com Pressão Negativa , Água do Mar , Vácuo , CicatrizaçãoRESUMO
BACKGROUND/AIMS: Treatments targeting cancer stem cells (CSCs) are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined. METHODS: Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and ß-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and ß-catenin were used to inhibit autophagy and ß-catenin signaling pathway, respectively, as loss-of-function experiments. RESULTS: We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced ß-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on ß-catenin and cell viability, while increasing ß-catenin abolished the effects of GRh2 on autophagy and cell viability. CONCLUSION: Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through reduced the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and ß-catenin signaling.
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Antineoplásicos Fitogênicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Ginsenosídeos/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , beta Catenina/metabolismoRESUMO
Background: Numerous studies have suggested a correlation between gut microbiota and acne vulgaris; however, no specific causal link has been explored. Materials and methods: To investigate the possible causal relationship between gut microbiota and acne vulgaris, this study employed a large-scale genome-wide association study (GWAS) summary statistic. Initially, a two-sample Mendelian randomization (MR) analysis was utilized to identify the specific gut microflora responsible for acne vulgaris. We used the Inverse Variance Weighted (IVW) method as the main MR analysis method. Additionally, we assessed heterogeneity and horizontal pleiotropy, while also examining the potential influence of individual single-nucleotide polymorphisms (SNPs) on the analysis results. In order to eliminate gut microbiota with reverse causal associations, we conducted reverse MR analysis. Multivariate Mendelian randomization analysis (MVMR) was then employed to verify the independence of the causal associations. Finally, we performed SNP annotation on the instrumental variables of independent gut microbiota and acne vulgaris to determine the genes where these genetic variations are located. We also explored the biological functions of these genes through enrichment analysis. Result: The IVW method of forward MR identified nine gut microbes with a causal relationship with acne vulgaris (p < 0.05). The findings from the sensitivity analysis demonstrate the absence of heterogeneity or horizontal pleiotropy, and leave-one-out analysis indicates that the results are not driven by a single SNP. Additionally, the Reverse MR analysis excluded two reverse-correlated pathogenic gut microbes. And then, MVMR was used to analyze seven gut microbes, and it was found that Cyanobacterium and Family XIII were risk factors for acne vulgaris, while Ruminococcus1 and Ruminiclostridium5 were protective factors for acne vulgaris. After conducting biological annotation, we identified six genes (PLA2G4A, FADS2, TIMP17, ADAMTS9, ZC3H3, and CPSF4L) that may be associated with the pathogenic gut microbiota of acne vulgaris patients. The enrichment analysis results indicate that PLA2G4A/FADS2 is associated with fatty acid metabolism pathways. Conclusion: Our study found independent causal relationships between four gut microbes and acne vulgaris, and revealed a genetic association between acne vulgaris patients and gut microbiota. Consider preventing and treating acne vulgaris by interfering with the relative content of these four gut microbes.
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BACKGROUND: Lipids, as a fundamental cell component, play an regulating role in controlling the different cellular biological processes involved in viral infections. A notable feature of coronavirus disease 2019 (COVID-19) is impaired lipid metabolism. The function of lipophagy-related genes in COVID-19 is unknown. The present study aimed to investigate biomarkers and drug targets associated with lipophagy and lipophagy-based therapeutic agents for COVID-19 through bioinformatics analysis. METHODS: Lipophagy-related biomarkers for COVID-19 were identified using machine learning algorithms such as random forest, Support Vector Machine-Recursive Feature Elimination, Generalized Linear Model, and Extreme Gradient Boosting in three COVID-19-associated GEO datasets: scRNA-seq (GSE145926) and bulk RNA-seq (GSE183533 and GSE190496). The cMAP database was searched for potential COVID-19 medications. RESULTS: The lipophagy pathway was downregulated, and the lipid droplet formation pathway was upregulated, resulting in impaired lipid metabolism. Seven lipophagy-related genes, including ACADVL, HYOU1, DAP, AUP1, PRXAB2, LSS, and PLIN2, were used as biomarkers and drug targets for COVID-19. Moreover, lipophagy may play a role in COVID-19 pathogenesis. As prospective drugs for treating COVID-19, seven potential downregulators (phenoxybenzamine, helveticoside, lanatoside C, geldanamycin, loperamide, pioglitazone, and trichostatin A) were discovered. These medication candidates showed remarkable binding energies against the seven biomarkers. CONCLUSIONS: The lipophagy-related genes ACADVL, HYOU1, DAP, AUP1, PRXAB2, LSS, and PLIN2 can be used as biomarkers and drug targets for COVID-19. Seven potential downregulators of these seven biomarkers may have therapeutic effects for treating COVID-19.
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Antivirais , Biomarcadores , Tratamento Farmacológico da COVID-19 , COVID-19 , Metabolismo dos Lipídeos , SARS-CoV-2 , Humanos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , SARS-CoV-2/genética , COVID-19/virologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Antivirais/uso terapêutico , Antivirais/farmacologia , Biologia Computacional/métodos , Aprendizado de Máquina , Lactamas Macrocíclicas/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Ácidos Hidroxâmicos/farmacologia , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêuticoRESUMO
In individuals with acne vulgaris, alterations occur in serum metabolite composition, yet the exact causal link between these metabolites and acne development remains elusive. Using genome-wide association datasets, we performed bidirectional Mendelian randomization (MR) to investigate the potential causal relationship between 309 serum metabolites and acne vulgaris. We performed sensitivity analysis to evaluate the presence of heterogeneity and pleiotropy. Forward MR analysis found 14 serum metabolites significantly associated with acne vulgaris, and reverse MR analysis found no significant association between acne vulgaris and these serum metabolites. Through validation using data from the FinnGen database of acne vulgaris studies, we found a conclusive and significant correlation between stearoylcarnitine and acne vulgaris. This provides new evidence in the search for new targets for the treatment of acne vulgaris.
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Acne Vulgar , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Acne Vulgar/genética , Acne Vulgar/sangue , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The wet flue gas desulfurization (WFGD) system of coal-fired power plants shows a good removal effect on condensable particulate matter (CPM), reducing the dust removal pressure for the downstream flue gas purification devices. In this work, the removal effect of a WFGD system on CPM and its organic pollutants from a coal-fired power plant was studied. By analyzing the organic components of the by-products emitted from the desulfurization tower, the migration characteristics of organic pollutants in gas, liquid, and solid phases, as well as the impact of desulfurization towers on organic pollutants in CPM, were discussed. Results show that more CPM in the flue gas was generated by coal-fired units at ultra-low load, and the WFGD system had a removal efficiency nearly 8% higher than that at full load. The WFGD system had significant removal effect on two typical esters, especially phthalate esters (PAEs), with the highest removal efficiency of 49.56%. In addition, the WFGD system was better at removing these two esters when the unit was operating at full load. However, it had a negative effect on n-alkanes, which increased the concentration of n-alkanes by 8.91 to 19.72%. Furthermore, it is concluded that the concentration distribution of the same type of organic pollutants in desulfurization wastewater was similar to that in desulfurization slurry, but quite different from that in coal-fired flue gas. The exchange of three organic pollutants between flue gas and desulfurization slurry was not significant, while the concentration distribution of organic matters in gypsum was affected by coal-fired flue gas.