ABSTRACT
Ice-covered transmission lines seriously affect the normal operation of the power transmission system. Resonance deicing based on different ice thicknesses is an effective method to solve the issue of ice-covered transmission lines. In order to obtain accurate ice thickness of transmission lines, this paper designs an ice thickness of transmission line recognition model based on Global Micro Strip Awareness Net (GMSA-Net) and proposes a Mixed Strip Convolution Module (MSCM) and a global micro awareness module (GMAM). The MSCM adapts to the shape of ice-covered transmission lines by using strip convolutions with different receptive fields, improving the encoder's ability to extract ice-covered features; the GMAM perceives through both global and micro parts, mining the connections between semantic information. Finally, the ice thickness of the generated segmented image is calculated using the method of regional pixel statistics. Experiments are conducted on the dataset of ice-covered transmission lines. The mean Intersection over Union (mIoU) of image segmentation reaches 96.4%, the balanced F-Score (F1-Score) is 98.1%, and the identification error of ice thickness is within 3.8%. Experimental results prove that this method can accurately identify the ice thickness of transmission lines, providing a control basis for the application of resonant deicing engineering.
ABSTRACT
Naphthoquine is a promising candidate for antimalarial combination therapy. Its combination with artemisinin has demonstrated excellent efficacy in clinical trials conducted across various malaria-endemic areas. A co-formulated combination of naphthoquine and azithromycin has also shown high clinical efficacy for malaria prophylaxis in Southeast Asia. Developing new combination therapies using naphthoquine will provide additional arsenal responses to the growing threat of artemisinin resistance. Furthermore, due to its long half-life, the possible interaction of naphthoquine with other drugs also needs attention. However, studies on its pharmacodynamic interactions with other drugs are still limited. In this study, the in vitro interactions of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen were evaluated in the asexual stage of Plasmodium falciparum 3D7. By using the combination index analysis and the SYBR Green I-based fluorescence assay, different interaction patterns of selected drugs with naphthoquine were revealed. Curcumin showed a slight but significant synergistic interaction with naphthoquine at lower effect levels, and no antagonism was observed across the full range of effect levels for all tested ratios. Atovaquone showed a potency decline when combined with naphthoquine. For ivermectin, a significant antagonism with naphthoquine was observed at a broad range of effect levels below 75% inhibition, although no significant interaction was observed at higher effect levels. Ketotifen interacted with naphthoquine similar to ivermectin, but significant antagonism was observed for only one tested ratio. These findings should be helpful to the development of new naphthoquine-based combination therapy and the clinically reasonable application of naphthoquine-containing therapies. IMPORTANCE: Pharmacodynamic interaction between antimalarials is not only crucial for the development of new antimalarial combination therapies but also important for the appropriate clinical use of antimalarials. The significant synergism between curcumin and naphthoquine observed in this study suggests the potential value for further development of new antimalarial combination therapy. The finding of a decline in atovaquone potency in the presence of naphthoquine alerts to a possible risk of treatment or prophylaxis failure for atovaquone-proguanil following naphthoquine-containing therapies. The observation of antagonism between naphthoquine and ivermectin raised a need for concern about the applicability of naphthoquine-containing therapy in malaria-endemic areas with ivermectin mass drug administration deployed. Considering the role of atovaquone-proguanil as a major alternative when first-line artemisinin-based combination therapy is ineffective and the wide implementation of ivermectin mass drug administration in malaria-endemic countries, the above findings will be important for the appropriate clinical application of antimalarials involving naphthoquine-containing therapies.
Subject(s)
Antimalarials , Atovaquone , Curcumin , Drug Interactions , Ivermectin , Ketotifen , Naphthoquinones , Plasmodium falciparum , Plasmodium falciparum/drug effects , Atovaquone/pharmacology , Antimalarials/pharmacology , Naphthoquinones/pharmacology , Humans , Curcumin/pharmacology , Ivermectin/pharmacology , Ketotifen/pharmacology , Drug Synergism , Aminoquinolines/pharmacology , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , 1-Naphthylamine/analogs & derivativesABSTRACT
The Crumbs protein (CRB) family plays a crucial role in maintaining the apical-basal polarity and integrity of embryonic epithelia. The family comprises different isoforms in different animals and possesses diverse structural, localization, and functional characteristics. Mutations in the human CRB1 or CRB2 gene may lead to a broad spectrum of retinal dystrophies. Various CRB-associated experimental models have recently provided mechanistic insights into human CRB-associated retinopathies. The knowledge obtained from these models corroborates the importance of CRB in retinal development and maintenance. Therefore, complete elucidation of these models can provide excellent therapeutic prospects for human CRB-associated retinopathies. In this review, we summarize the current animal models and human-derived models of different CRB family members and describe the main characteristics of their retinal phenotypes.
Subject(s)
Membrane Proteins , Retinal Diseases , Humans , Animals , Membrane Proteins/genetics , Membrane Proteins/metabolism , Retinal Diseases/genetics , Retinal Diseases/pathology , Retinal Diseases/metabolism , Retina/metabolism , Retina/pathology , Eye Proteins/genetics , Eye Proteins/metabolism , Disease Models, Animal , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , MutationABSTRACT
Engrailed-1 (EN1) is a developmental gene that encodes En1, a highly conserved transcription factor involved in regionalization during early embryogenesis and in the later maintenance of normal neurons. After birth, EN1 still plays a role in the development and physiology of the body; for example, it exerts a protective effect on midbrain dopaminergic (mDA) neurons, and loss of EN1 causes mDA neurons in the ventral midbrain to gradually die approximately 6 weeks after birth, resulting in motor and nonmotor symptoms similar to those observed in Parkinson's disease. Notably, EN1 has been identified as a possible susceptibility gene for idiopathic Parkinson's disease in humans. EN1 is involved in the processes of wound-healing scar production and tissue and organ fibrosis. Additionally, EN1 can lead to tumorigenesis and thus provides a target for the treatment of some tumors. In this review, we summarize the effects of EN1 on embryonic organ development, describe the consequences of the deletion or overexpression of the EN1 gene, and discuss the pathways in which EN1 is involved. We hope to clarify the role of EN1 as a developmental gene and present potential therapeutic targets for diseases involving the EN1 gene.
Subject(s)
Homeodomain Proteins , Parkinson Disease , Humans , Homeodomain Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Neurons/metabolism , Gene Expression Regulation , Genes, Homeobox , Parkinson Disease/genetics , Parkinson Disease/metabolism , Parkinson Disease/pathologyABSTRACT
Melatonin (MT), an indoleamine compound, has a pleiotropic effect on plant growth and development and can regulate the quality of tree fruit. Systematic research on the effect of preharvest MT spraying on pear fruit quality and technical solutions for MT application to regulate pear fruit quality are still lacking. Thus, here we aimed to evaluate the effects of different spraying times, concentrations, and exogenous MT application times on 'Yuluxiang' pear fruit quality. Our results showed that the single fruit weight and vertical and horizontal diameters of pear fruit sprayed with MT twice at 30 and 90 d after full bloom were the largest, and the red and green values of the treatment were the highest. MT-treated pears had higher contents of total soluble solids, soluble sugar, sucrose, sorbitol, fructose, and glucose and lower contents of titratable acid, malic acid, and citric acid. Moreover, exogenous MT treatment increased the pear peel strength. Based on the principal component analysis of 10 fruit quality indices, the suitable periods for MT spraying on 'Yuluxiang' pears were 30 and 90 d after full bloom, the suitable concentration was 100 µmol/L, and the suitable number of times was two. This study provides a theoretical reference for optimizing MT application and improving pear fruit quality.
ABSTRACT
BACKGROUND: In diabetic retinopathy, increasing evidence points to a link between the pathogenesis of retinal microangiopathy and the endothelial cell-specific factor roundabout4 (ROBO4). According to earlier research, specificity protein 1 (SP1) enhances the binding to the ROBO4 promoter, increasing Robo4 expression and hastening the progression of diabetic retinopathy. To determine if this is related to aberrant epigenetic modifications of ROBO4, we examined the methylation level of the ROBO4 promoter and the corresponding regulatory mechanism during the course of diabetic retinopathy and explored the effect of this mechanism on retinal vascular leakage and neovascularization. METHODS: The methylation level of CpG sites in the ROBO4 promoter was detected in human retinal endothelial cells (HRECs) cultured under hyperglycemic conditions and retinas from streptozotocin-induced diabetic mice. The effects of hyperglycemia on DNA methyltransferase 1, Tet methylcytosine dioxygenase 2 (TET2), 5-methylcytosine, 5-hydroxymethylcytosine, and the binding of TET2 and SP1 to the ROBO4 promoter, as well as the expression of ROBO4, zonula occludens 1 (ZO-1) and occludin were examined. Short hairpin RNA was used to suppress the expression of TET2 or ROBO4 and the structural and functional changes in the retinal microvascular system were assessed. RESULTS: In HRECs cultured under hyperglycemic conditions, the ROBO4 promoter methylation level decreased. Hyperglycemia-induced TET2 overexpression caused active demethylation of ROBO4 by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, which enhanced the binding of SP1 to ROBO4, increased the expression of ROBO4, and decreased the expression of ZO-1 and occludin, leading to the abnormalities in monolayer permeability, migratory ability and angiogenesis of HRECs. The above pathway was also demonstrated in the retinas of diabetic mice, which caused leakage from retinal capillaries and neovascularization. Inhibition of TET2 or ROBO4 expression significantly ameliorated the dysfunction of HRECs and retinal vascular abnormalities. CONCLUSIONS: In diabetes, TET2 can regulate the expression of ROBO4 and its downstream proteins by mediating active demethylation of the ROBO4 promoter, which accelerates the development of retinal vasculopathy. These findings suggest that TET2-induced ROBO4 hypomethylation is a potential therapeutic target, and anti- TET2/ROBO4 therapy is anticipated to emerge as a novel strategy for early intervention and delayed progression of diabetic retinopathy.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Dioxygenases , Hyperglycemia , Animals , Humans , Mice , 5-Methylcytosine , Diabetes Mellitus, Experimental/genetics , Diabetic Retinopathy/genetics , DNA-Binding Proteins/genetics , Endothelial Cells , Neovascularization, Pathologic , Occludin , Receptors, Cell SurfaceABSTRACT
Introduction: Respirators chosen based on their assigned protection factor (APF) enable wearers to effectively reduce particulate matter concentrations to safe levels when used correctly. As a crucial factor in achieving the intended APF, the fit test has become a necessary procedure in respiratory disease protection. Methods: This study involved 225 participants who underwent a fit test using two reusable types of half masks and two types of full masks. Condensation nuclei counting (CNC) and controlled negative pressure (CNP) were performed. Results: The results revealed that the passing rate of full masks was higher compared to half masks. Specifically, the passing rate for the half masks and the full masks were 84.7 and 91.6%, respectively. Gender exerted a statistically significant effect on the passing rate. Nevertheless, age, educational background, and training exhibited relatively negligible effects. Certain movements, such as facing forward, were identified as key actions with strong correlation. Additionally, talking was considered a key action with a high failure rate due to instantaneous leakages. Most participants failed at the initial step of CNP, but nearly all of them passed the fit test using CNC. Discussion: Therefore, putting on full masks, especially for women, provides optimal protection during work. Furthermore, attention should be given to the displacement and deformation of the respirator during the key actions. When it comes to fit test methods, CNC was found to be more practical and comprehensive compared to CNP. Moreover, additional physiological characteristics, such as double chins, could be explored as potential influential factors.
Subject(s)
Occupational Exposure , Respiratory Protective Devices , Humans , Female , Occupational Exposure/prevention & control , Particulate MatterABSTRACT
The double-stranded DNA (dsDNA) viruses represented by adenovirus and monkeypox virus, have attracted widespread attention due to their high infectivity. In 2022, the global outbreak of mpox (or monkeypox) has led to the declaration of a Public Health Emergency of International Concern. However, to date therapeutics approved for dsDNA virus infections remain limited and there are still no available treatments for some of these diseases. The development of new therapies for treating dsDNA infection is in urgent need. In this study, we designed and synthesized a series of novel disulfide-incorporated lipid conjugates of cidofovir (CDV) as potential candidates against dsDNA viruses including vaccinia virus (VACV) and adenovirus (AdV) 5. The structure-activity relationship analyses revealed that the optimum linker moiety was C2H4 and the optimum aliphatic chain length was 18 or 20 atoms. Among the synthesized conjugates, 1c exhibited more potency against VACV (IC50 = 0.0960 µM in Vero cells; IC50 = 0.0790 µM in A549 cells) and AdV5 (IC50 = 0.1572 µM in A549 cells) than brincidofovir (BCV). The transmission electron microscopy (TEM) images revealed that the conjugates could form micelles in phosphate buffer. The stability studies in the GSH environment demonstrated that the formation of micelles in phosphate buffer might protect the disulfide bond from glutathione (GSH) reduction. The dominant means of the synthetic conjugates to liberate the parent drug CDV was by enzymatic hydrolysis. Furthermore, the synthetic conjugates remained sufficiently stable in simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and pooled human plasma, which indicated the possibility for oral administration. These results indicated 1c may be a broad-spectrum antiviral candidate against dsDNA viruses with potential oral administration. Moreover, modification of the aliphatic chain attached to the nucleoside phosphonate group was involved as an efficient prodrug strategy for the development of potent antiviral candidates.
Subject(s)
Antiviral Agents , Prodrugs , Animals , Chlorocebus aethiops , Humans , Cidofovir/pharmacology , Antiviral Agents/chemistry , Prodrugs/pharmacology , Vero Cells , Micelles , Cytosine/pharmacology , Cytosine/chemistry , Vaccinia virus , Lipids , PhosphatesABSTRACT
Sports biomechanics is the study of the mechanical principles of human movement and how they apply to sports performance [...].
ABSTRACT
INTRODUCTION: The purpose of this study was to evaluate the long-term outcomes of posterior capsular opacification (PCO) in highly myopic eyes and its influencing factors. METHODS: Patients undergoing phacoemulsification with intraocular lens implantation and followed up for 1-5 years were included in this prospective cohort study. The severity of PCO was evaluated using EPCO2000 software system, with the area of central 3.0 mm (PCO-3 mm) and within the capsulorhexis (PCO-C) both being analyzed. Percentage of eyes after Nd:YAG capsulotomy, as well as clinically significant PCO (defined as eyes with visual-impairing PCO or after capsulotomy), were also included as outcome variables. RESULTS: A total of 673 highly myopic eyes [axial length (AL) ≥ 26 mm] and 224 control eyes (AL < 26 mm) were analyzed. The mean follow-up time was 34.0 ± 9.0 months. PCO was more severe in highly myopic eyes compared with controls with regard to higher EPCO scores (P < 0.001 for both PCO-3 mm and PCO-C), higher capsulotomy rate (P = 0.001), higher clinically significant PCO rate (P < 0.001) and shorter PCO-free survival time (P < 0.001). Extreme myopia (AL ≥ 28 mm) would further aggravate PCO in terms of higher EPCO scores (PCO-3 mm: P = 0.017; PCO-C: P = 0.013) and higher clinically significant PCO rate (P = 0.024) compared with other myopic eyes. In highly myopic eyes, AL [odds ratio (OR) 1.124, P = 0.004] and follow-up duration (OR 1.082, P < 0.001) were independent risk factors for clinically significant PCO after cataract surgery. CONCLUSION: Highly myopic eyes had more severe PCO in the long term. Longer AL and follow-up duration were associated with higher risk of PCO. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT03062085).
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ABSTRACTThe main protease (3-chymotrypsin-like protease, 3CLpro) of SARS-CoV-2 has become a focus of anti-coronavirus research. Despite efforts, drug development targeting 3CLpro has been hampered by limitations in the currently available activity assays. Additionally, the emergence of 3CLpro mutations in circulating SARS-CoV-2 variants has raised concerns about potential resistance. Both emphasize the need for a more reliable, sensitive, and facile 3CLpro assay. Here, we report an orthogonal dual reporter-based gain-of-signal assay for measuring 3CLpro activity in living cells. It builds on the finding that 3CLpro induces cytotoxicity and reporter expression suppression, which can be rescued by its inhibitor or mutation. This assay circumvents most limitations in previously reported assays, especially false positives caused by nonspecific compounds and signal interference from test compounds. It is also convenient and robust for high throughput screening of compounds and comparing the drug susceptibilities of mutants. Using this assay, we screened 1789 compounds, including natural products and protease inhibitors, with 45 compounds that have been reported to inhibit SARS-CoV-2 3CLpro among them. Except for the approved drug PF-07321332, only five of these inhibit 3CLpro in our assays: GC376; PF-00835231; S-217622; Boceprevir; and Z-FA-FMK. The susceptibilities of seven 3CLpro mutants prevalent in circulating variants to PF-07321332, S-217622, and GC376 were also assessed. Three mutants were identified as being less susceptible to PF-07321322 (P132H) and S-217622 (G15S, T21I). This assay should greatly facilitate the development of novel 3CLpro-targeted drugs and the monitoring of the susceptibility of emerging SARS-CoV-2 variants to 3CLpro inhibitors.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Mutation , Peptide Hydrolases , Antiviral Agents/pharmacologyABSTRACT
Ketones are among the most useful functional groups in organic synthesis, and they are commonly encountered in a broad range of compounds with various applications. Herein, we describe the mesoionic carbene-catalyzed coupling reaction of aldehydes with non-activated secondary and even primary alkyl halides. This metal-free method utilizes deprotonated Breslow intermediates derived from mesoionic carbenes (MICs), which act as super electron donors and induce the single-electron reduction of alkyl halides. This mild coupling reaction has a broad substrate scope and tolerates many functional groups, which allows to prepare a diversity of simple ketones as well as bio-active molecules by late-stage functionalization.
ABSTRACT
The Lassa virus (LASV) causes Lassa fever, a highly infectious and lethal agent of acute viral hemorrhagic fever. At present, there are still no effective treatments available, creating an urgent need to develop novel therapeutics. Some benzimidazole compounds targeting the arenavirus envelope glycoprotein complex (GPC) are promising inhibitors of LASV. In this study, we synthesized two series of LASV inhibitors based on the benzimidazole structure. Lentiviral pseudotypes bearing the LASV GPC were established to identify virus entry inhibitors. Surface plasmon resonance (SPR) was further used to verify the binding activities of the potential compounds. Compounds 7d-Z, 7h-Z, 13c, 13d, and 13f showed relatively excellent antiviral activities with IC50 values ranging from 7.58 to 15.46 nM and their SI values above 1251. These five representative compounds exhibited stronger binding affinity with low equilibrium dissociation constants (KD < 8.25 × 10-7 M) in SPR study. The compound 7h-Z displayed the most potent antiviral activity (IC50 = 7.58 nM) with a relatively high SI value (2496), which could be further studied as a lead compound. The structure-activity relationship indicated that the compounds with lipophilic and spatially larger substituents might possess higher antiviral activity and a much larger safety margin. This study will provide some good guidance for the development of highly active compounds with a novel skeleton against LASV.
Subject(s)
Arenavirus , Lassa Fever , Humans , Lassa virus , Lassa Fever/drug therapy , Antiviral Agents/pharmacology , Benzimidazoles/pharmacologyABSTRACT
Infection with Yersinia pestis (Y. pestis) may cause pneumonic plague, which is inevitably fatal without treatment. Gentamicin (GM), an aminoglycoside antibiotic, is a drug commonly used in the treatment of plague. However, it requires repeated intramuscular or intravenous administration. Pulmonary drug delivery is noninvasive, with the advantages of local targeting and reduced risk of systemic toxicity. In this study, GM powders were prepared using spray-drying technology. The powders displayed good physical and chemical properties and met the requirements for human pulmonary inhalation. The formulation of the powders was optimized using a 32 full factorial design. A formulation of 15% (w/w) of L-leucine was prepared, and the spray-drying process parameters using an inlet temperature of 120°C and a 15% pump rate were determined to produce the best powder. In addition, the optimized GM spray-dried powders were characterized in terms of morphology, crystallinity, powder fluidity, and aerodynamic particle size distribution analysis. In a mouse model of pneumonic plague, we compared the therapeutic effects among three administration routes, including subcutaneous injection, liquid atomization, and dry powder atomization. In conclusion, our data suggest that inhalation therapy with GM spray-dried powders is an effective treatment for pneumonic plague.
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Fintech risks commercial banks in three ways, particularly operational efficiency, financial innovation, and risk management. Based on the data of 37 Chinese-listed commercial banks from 2011 to 2020, the study empirically analyzes the impact of fintech on bank risk-taking, and the intermediary effects of the three channels, such as operational efficiency, financial innovation, and risk management. The results show that fintech can effectively reduce the risk of banks. The results of heterogeneity analysis revealed that fintech strongly affects the risk-taking of state-owned banks but not obviously for rural commercial banks. Financial efficiency, financial innovation, and risk management indirectly affect the risk-taking of banks that contributed 8.51, 7.18, and 5.77%, respectively. We also constructed the commercial bank risk-warning index. Based on the quarterly data of banks from 2011 to 2020, we empirically tested the early warning effect of the bank risk-warning index. The results showed that when the signal month is set to 12 months, the bank risk-warning index can have a warning effect in this period.
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Despite considerable advances in prevention, diagnosis, and therapy, nephrotic syndrome (NS) remains a significant cause of high morbidity and mortality globally. As a result, there is an urgent need to identify novel effective preventative and therapeutic agents for NS. NS is implicated in glomerular permselectivity injury, which can be attributed to oxidative distress, inflammation, lipid nephrotoxicity, podocyte apoptosis, autophagy dysfunction, and slit diaphragm (SLD) dysfunction. In addition to its well-documented antioxidant potency, procyanidin B2 (PB2) may exhibit pleiotropic effects by targeting various canonical signaling events, such as NF-κB, PPARs, PI3K/Akt, mTOR, and the caspase family. As a result, PB2 may be a promising therapeutic target against NS. To test this hypothesis, we established an Adriamycin (ADR)-induced NS mouse model to evaluate the pleiotropic renoprotective effects of PB2 on NS. Here, we demonstrated that PB2 improves podocyte injury via inhibition of NOX4/ROS and Hsp90/NF-κB to exhibit antioxidant and anti-inflammatory potency, respectively. We also show that PB2 indirectly activates the PI3K/Akt axis by regulating SLD protein levels, resulting in normalized podocyte apoptosis and autophagy function. Further, loss of albumin (ALB) induces lipid nephrotoxicity, which we found to be alleviated by PB2 via activation of PPARα/ß-mediated lipid homeostasis and the cholesterol efflux axis. Interestingly, our results also suggested that PB2 reduces electrolyte abnormalities and edema. In addition, PB2 may contribute protective effects against trace element dys-homeostasis, which, through alleviating serum ALB loss, leads to a protective effect on glomerular permselectivity injury. Taken together, our results reveal that the identified mechanisms of PB2 on NS are multifactorial and involve inhibition of oxidative distress and inflammatory responses, as well as improvements in podocyte apoptosis and autophagy dysfunction, amelioration of lipid nephrotoxicity, and modulation of electrolyte abnormalities and edema. Thus, we provide a theoretical basis for the clinical application of PB2 against NS.
Subject(s)
Kidney Diseases , Nephrotic Syndrome , Podocytes , Animals , Antioxidants/metabolism , Apoptosis , Biflavonoids , Catechin , Doxorubicin/toxicity , Electrolytes/adverse effects , Electrolytes/metabolism , Kidney Diseases/metabolism , Lipids/pharmacology , Mice , NF-kappa B/genetics , NF-kappa B/metabolism , Nephrotic Syndrome/chemically induced , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Podocytes/metabolism , Proanthocyanidins , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
We compared intestinal microbes in anterior noninfectious scleritis patients with and without rheumatoid arthritis. Active noninfectious anterior scleritis patients without other immune diseases (G group, 16 patients) or with active rheumatoid arthritis (GY group, seven patients) were included in this study. Eight age- and sex-matched healthy subjects served as controls (N group). DNA was extracted from fecal samples. The V3-V4 16S rDNA region was amplified and sequenced by high-throughput 16S rDNA analysis, and microbial contents were determined. A significant decrease in species richness in the GY group was revealed by α- and ß-diversity analyses (p = 0.02 and p = 0.004, respectively). At the genus level, 14 enriched and 10 decreased microbes in the G group and 13 enriched and 18 decreased microbes in the GY group were identified. Among them, four microbes were enriched in both the G and GY groups, including Turicibacter, Romboutsia, Atopobium, and Coprobacillus. Although two microbes (Lachnospiraceae_ND3007_group and Eggerthella) exhibited similar tendencies in the G and GY groups, changes in these microbes were more significant in the GY group (p < 0.05). Interaction analysis showed that Intestinibacter, Romboutsia, and Turicibacter, which were enriched in both the G and GY groups, correlated positively with each other. In addition, nine microbes were decreased in the GY group, which demonstrates a potential protective role for these microbes in the pathogenesis of scleritis via interactions with each other.
ABSTRACT
Tri-(2,3-dibromopropyl) isocyanate (TBC), a new emerged persistent organic pollutant, is widely used in fields of flame retardant, textile, rubber and plastic with strong hepatotoxicity. Purple Sweet Potato Polysaccharide (PSPP) has antioxidant and hepatoprotective effects. This study aims to answer the scientific question whether PSPP has a protective effect on TBC induced liver injury. The effect of PSPP on the apoptosis of HepG2 cells was detected by MTT assay, the morphological changes were observed by morphological observation, and the apoptosis rate was determined by flow cytometry. The apoptotic genes were detected by qPCR assay, the relevant protein express was detected by western blot. The correlation between proteins and genes in the apoptosis pathway of HepG2 cells was calculated. To further reveal the apoptosis mechanism of TBC hepatotoxicity in vivo, 19 target genes and 14 apoptotic related proteins of inhibiting apoptosis via death receptor and mitochondria were discussed, all the above results proved that PSPP had protective effect on liver injury induced by TBC. This study not only provided a scientific basis for clarifying the mechanism of TBC hepatotoxicity and the protective effect of PSPP, but also generated the new point and method in terms of the prevention in advance and early intervention of diseases caused by environmental pollution.
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Dietary Carbohydrates/pharmacology , Ipomoea batatas/metabolism , Isocyanates/toxicity , Polysaccharides/pharmacology , Hep G2 Cells , HumansABSTRACT
The sole is a key component of the interaction between foot and ground in daily activities, and its cushioning performance plays a crucial role in protecting the joints of lower limbs from impact injuries. Based on the excellent cushioning performance of the ostrich foot and inspired by the structure and material assembly features of the ostrich foot's metatarsophalangeal skeletal-tendon and the ostrich toe pad-fascia, a functional bionic cushioning unit for the midsole (including the forefoot and heel) area of athletic shoes was designed using engineering bionic technology. The bionic cushioning unit was then processed based on the bionic design model, and the shoe soles were tested with six impact energies ranging from 3.3 J to 11.6 J for a drop hammer impact and compared with the conventional control sole of the same size. The results indicated that the bionic forefoot area absorbed 9.83-34.95% more impact and 10.65-43.84% more energy than the conventional control forefoot area, while the bionic heel area absorbed 26.34-44.29% more impact and 28.1-51.29% more energy than the conventional control heel area when the controlled impact energy varied from 3.3 J to 11.6 J. The cushioning performance of the bionic cushioning sole was generally better than that of the conventional control sole, and the cushioning and energy-absorption performances of the heel bionic cushioning unit were better than those of the forefoot bionic cushioning unit. This study provides innovative reference and research ideas for the design and development of sports shoes with good cushioning performance.
ABSTRACT
Osteosarcoma is a commonly occurring bone malignancy, and it is the second most common cause of cancer deaths in adolescents and children. A sensitive silica nanoparticle (Si-NP) modified current-volt sensor was introduced to identify the osteopontin antigen, a well-known biomarker for osteosarcoma. Si-NP was extracted from the rice husk ash and utilized for the surface functionalization on the interdigitated microelectrode sensing surface. Extracted Si-NP has a spherical shape with uniform distribution, and it is confirmed by field emission scanning electron microscopy and field-emission transmission electron microscopy. Si-NP was layered on the electrode surface through a (3-aminopropyl)triethoxysilane amine linker, and the antibody was immobilized on Si-NP through a glutaraldehyde linker. Osteopontin was effectively detected on the antibody-attached surface, and the determination limit was 0.6 ng/mL. The regression was determined as y = 0.9366x - 1.1113 and the R2 value was 0.9331 and the detection limit of osteopontin was 0.6 ng/mL in the range between 0.3 and 5 ng/mL. In addition, control performance with nonimmune antibodies and albumin did not change the current volt, showing the specific osteopontin identification. This research work brings out the easy and cost-effective method to diagnose osteosarcoma and its etiology.