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AIMS: To investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE). MATERIALS AND METHODS: Through inducing Spk inflammation in murine models, leukocyte migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction. KEY FINDINGS: Spk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as ß2 integrin, PI3K, and PAD2 due to its intermolecular coupling. SIGNIFICANCE: Our results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.
Subject(s)
COVID-19 , Cell Movement , Diminazene , Extracellular Traps , Inflammation , Leukocytes , SARS-CoV-2 , Diminazene/pharmacology , Diminazene/analogs & derivatives , Animals , Mice , Humans , Cell Movement/drug effects , Extracellular Traps/metabolism , Extracellular Traps/drug effects , Leukocytes/metabolism , Leukocytes/drug effects , SARS-CoV-2/drug effects , Inflammation/metabolism , Inflammation/drug therapy , COVID-19/metabolism , Male , COVID-19 Drug Treatment , Cell Adhesion/drug effects , Oxidative Stress/drug effects , Spike Glycoprotein, CoronavirusABSTRACT
This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.
Subject(s)
COVID-19 Drug Treatment , Coronavirus 3C Proteases , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2 , SARS-CoV-2/drug effects , Humans , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Hydrogen Bonding , Ligands , COVID-19/virology , Protein BindingABSTRACT
This study evaluated the median lethal concentration of silver nanoparticles and their effects in fish tambaqui Colossoma macropomum. Therefore, an acute toxicity assay was carried out in completely randomized design evaluating six different concentrations of silver nanoparticles on blood parameters of tambaqui. The silver nanoparticles were produced by chemical reduction with polyvinyl alcohol (AgNP-PVA). The lethal concentration 50% (LC50) was estimated using probit regression. The blood was collected, analyzed and the data were submitted to T-test (dying x surviving fish) and Tukey test (surviving fish). An increase in glucose, hematocrit, total plasma protein, hemoglobin, erythrocytes, leukocytes, monocytes, and neutrophils as well as reduced MCV (mean corpuscular volume) in dying fish compared to surviving fish were observed. Survived fish exposed to 187.5 µg/L showed an increase in hematocrit, MCV, and MCH and a reduction in erythrocytes, total numbers of leukocyte, thrombocyte, lymphocyte, and neutrophil. The fish exposed to concentrations below 125 µg/L, had returned the blood parameter to baselines compared to control. The estimated LC50 was 165.09 µg/L and was classified as highly toxic for the fish tambaqui. In higher concentrations, it causes an acute respiratory toxicity, but in concentrations below 125 µg/L, the fish can adapt to the stressing agent.
Subject(s)
Characiformes , Metal Nanoparticles , Animals , Silver/toxicity , Metal Nanoparticles/toxicity , Blood Cells , ErythrocytesABSTRACT
Objective: To analyze the types and functions of CD34+ cells in full-thickness skin defect wounds of normal mice and diabetic mice by single-cell RNA sequencing. Methods: This study was an experimental study. The CD34+ cell lineage tracing mouse was produced, and the visualization of CD34+ cells under the fluorescent condition was realized. Six male CD34+ cell lineage tracing mice aged 7-8 weeks (designated as diabetic group) were intraperitoneally injected with streptozotocin to establish a diabetic model, and full-thickness skin defect wounds were prepared on their backs when they reached 13 weeks old. Another 6 male CD34+ cell lineage tracing mice aged 13 weeks (designated as control group) were also subjected to full-thickness skin defect wounds on their backs. On post-injury day (PID) 4, wound tissue was collected from 3 mice in control group and 2 mice in diabetic group, and digested to prepare single-cell suspensions. CD34+ cells were screened using fluorescence-activated cell sorting, followed by single-cell RNA sequencing. The Seurat 4.0.2 program in the R programming language was utilized for dimensionality reduction, visualization, and cell clustering analysis of CD34+ cell types, and to screen and annotate the marker genes for each CD34+ cell subpopulation. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis was performed to analyze the differentially expressed genes (DEGs) of CD34+ fibroblasts (Fbs), smooth muscle cells (SMCs), keratinocytes (KCs), and chondrocyte-like cells (CLCs) in the wound tissue of two groups of mice for exploring cellular functions. Results: On PID 4, CD34+ cells in the wound tissue of both groups of mice were consisted of 7 cell types, specifically endothelial cells, Fbs, KCs, macrophages, T cells, SMCs, and CLCs. Among these, Fbs were further classified into 5 subpopulations. Compared with those in control group, the proportions of CD34+ endothelial cells, Fbs subpopulation 1, Fbs subpopulation 4, KCs, and CLCs in the wound tissue of mice were increased in diabetic group, while the proportions of CD34+ Fbs subpopulation 2, Fbs subpopulation 3, and SMCs were decreased. The marker genes for annotating CD34+ CLCs, endothelial cells, Fbs subpopulation 1, Fbs subpopulation 2, Fbs subpopulation 3, Fbs subpopulation 4, Fbs subpopulation 5, KCs, macrophages, SMCs, and T cells were respectively metastasis-associated lung adenocarcinoma transcript 1, fatty acid binding protein 4, Gremlin 1, complement component 4B, H19 imprinted maternally expressed transcript, Dickkopf Wnt signaling pathway inhibitor 2, fibromodulin, keratin 5, CD74 molecule, regulator of G protein signaling 5, and inducible T-cell co-stimulator molecule. KEGG and GO enrichment analysis revealed that, compared with those in control group, DEGs with significant differential expression (SDE) in CD34+ Fbs from the wound tissue of mice in diabetic group on PID 4 were significantly enriched in terms related to inflammatory response, extracellular matrix (ECM) organization, regulation of cell proliferation, and aging (with Pvalues all <0.05), DEGs with SDE in CD34+ SMCs were significantly enriched in terms related to cell migration, apoptotic process, positive regulation of transcription, and phagosome (with P values all <0.05), DEGs with SDE in CD34+ KCs were significantly enriched in terms related to mitochondrial function, transcription, and neurodegenerative diseases (with P values all <0.05), and DEGs with SDE in CD34+ CLCs were significantly enriched in terms related to rhythm regulation, ECM, and viral infection (with P values all <0.05). Conclusions: CD34+ cells display high heterogeneity in the healing process of full-thickness skin defect wounds in both normal mice and diabetic mice. The significantly enriched functions of DEGs with SDE in CD34+ cell subpopulations in the wound tissue of the two mouse groups are closely related to the wound healing process.
Subject(s)
Diabetes Mellitus, Experimental , Skin , Soft Tissue Injuries , Animals , Male , Mice , Diabetes Mellitus, Experimental/genetics , Endothelial Cells , Sequence Analysis, RNA , Skin/injuries , Wound Healing/geneticsABSTRACT
The production of sustainable materials with properties aimed at the additive manufacturing of electrochemical sensors has gained prestige in the scientific scenario. Here, a novel lab-made composite material using graphite (G) and carbon nitride (C3N4) embedded into polylactic acid (PLA) biopolymer is proposed to produce 3D-printed electrodes. PLA offers printability and mechanical stability in this composition, while G and C3N4 provide electrical properties and electrocatalytic sites, respectively. Characterizations by Raman and infrared spectroscopies and Energy Dispersive X-rays indicated that the G/C3N4/PLA composite was successfully obtained, while electron microscopy images revealed non-homogeneous rough surfaces. Better electrochemical properties were achieved when the G/C3N4/PLA proportion (35:5:60) was used. As a proof of concept, amaranth (AMR), a synthetic dye, was selected as an analyte, and a fast method using square wave voltammetry was developed. Utilizing the 3D-printed G/C3N4/PLA electrode, a more comprehensive linear range (0.2 to 4.2 µmol/L), a 5-fold increase in sensitivity (9.83 µmol-1 L µA), and better limits of detection (LOD = 0.06 µmol/L) and quantification (LOQ = 0.18 µmol/L) were achieved compared to the G/PLA electrode. Samples of jelly, popsicles, isotonic drinks, and food flavoring samples were analyzed, and similar results to those obtained by UV-vis spectrometry confirmed the method's reliability. Therefore, the described sensor is a simple, cost-effective alternative for assessing AMR in routine food analysis.
Subject(s)
Amaranthus , Graphite , Nitriles , Nitrogen Compounds , Amaranth Dye , Reproducibility of Results , Electrodes , Polyesters , Printing, Three-Dimensional , Electrochemical TechniquesABSTRACT
We propose exploiting the superluminal plasma wake for coherent Cherenkov radiation by injecting a relativistic electron beam (REB) into a plasma with a slowly varying density up-ramp. Using three-dimensional particle-in-cell and far-field time-domain radiation simulations, we show that an isolated subcycle pulse is coherently emitted towards the Cherenkov angle by bubble-sheath electrons successively at the rear of the REB-induced superluminal plasma wake. A theoretical model based on a superluminal current dipole has been developed to interpret such coherent radiation, and agrees well with the simulation results. This radiation has ultrashort attosecond-scale duration and high intensity, and exhibits excellent directionality with ultralow angular divergence and stable carrier envelope phase. Its intensity increases with the square of the propagation length and its central frequency can be easily tuned over a wide range, from the far infrared to the ultraviolet.
ABSTRACT
Cutaneous tuberculosis is an infrequent form of extra-pulmonary tuberculosis, even in high-prevalence settings. We present the case of a patient living with advanced HIV who developed extensive cutaneous tuberculosis. The polymorphic skin lesions were the most striking clinical manifestation of underlying disseminated tuberculosis. Contribution: This case report highlights an unusual presentation of tuberculosis. Cutaneous tuberculosis has a wide spectrum of clinical presentations and may be under-recognised by clinicians. We recommend early biopsy for microbiological diagnosis.
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Propagation of high-current relativistic electron beam (REB) in plasma is relevant to many high-energy astrophysical phenomena as well as applications based on high-intensity lasers and charged-particle beams. Here, we report a new regime of beam-plasma interaction arising from REB propagation in medium with fine structures. In this regime, the REB cascades into thin branches with local density a hundred times the initial value and deposits its energy 2 orders of magnitude more efficiently than that in homogeneous plasma, where REB branching does not occur, of similar average density. Such beam branching can be attributed to successive weak scatterings of the beam electrons by the unevenly distributed magnetic fields induced by the local return currents in the skeletons of the porous medium. Results from a model for the excitation conditions and location of the first branching point with respect to the medium and beam parameters agree well with that from pore-resolved particle-in-cell simulations.
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When an epidemic started in the Chinese city of Wuhan in December 2019, coronavirus was identified as the cause. Infection by the virus occurs through the interaction of viral S protein with the hosts' angiotensin-converting enzyme 2. By leveraging resources such as the DrugBank database and bioinformatics techniques, ligands with potential activity against the SARS-CoV-2 spike protein were designed and identified in this investigation. The FTMap server and the Molegro software were used to determine the active site of the Spike-ACE2 protein's crystal structure. Virtual screening was performed using a pharmacophore model obtained from antiparasitic drugs, obtaining 2000 molecules from molport®. The ADME/Tox profiles were used to identify the most promising compounds with desirable drug characteristics. The binding affinity investigation was then conducted with selected candidates. A molecular docking study showed five structures with better binding affinity than hydroxychloroquine. Ligand_003 showed a binding affinity of -8.645 kcal·mol-1, which was considered an optimal value for the study. The values presented by ligand_033, ligand_013, ligand_044, and ligand_080 meet the profile of novel drugs. To choose compounds with favorable potential for synthesis, synthetic accessibility studies and similarity analyses were carried out. Molecular dynamics and theoretical IC50 values (ranging from 0.459 to 2.371 µM) demonstrate that these candidates are promising for further tests. Chemical descriptors showed that the candidates had strong molecule stability. Theoretical analyses here show that these molecules have potential as SARS-CoV-2 antivirals and therefore warrant further investigation.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Molecular Docking Simulation , Angiotensin-Converting Enzyme 2 , Ligands , Molecular Dynamics Simulation , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Protein BindingABSTRACT
Objective: To analyze the impact of malignant neoplasms, cardiovascular diseases, respiratory diseases and diabetes (four major chronic diseases) on the increase of life expectancy of local population in Ji'nan during 2015-2020. Methods: Based on 2015-2020 cause-of-death surveillance information and population data of Ji'nan, we used abbreviated life expectancy table and Arriaga decomposition method to analyze the overall and disease specific contributions of four major chronic diseases to the increase of life expectancy, and the gender and age specific contributions of mortality rates of four major chronic diseases to the increase of life expectancy of local population from 2015 to 2020. Results: Life expectancy of the local population in Ji'nan increased by 1.59 years from 2015 to 2020. The decline in mortality rates of the four major chronic diseases contributed 1.25 years, with a contribution of 78.62%. The life expectancy in men increased by 1.66 years, with a contribution of 1.18 years from the decline in mortality rate of four major chronic diseases, and the life expectancy in women increased by 1.52 years, with a contribution of 1.35 years from the decline in mortality of four major chronic diseases. The declines in the mortality rates of malignant neoplasms, cardiovascular diseases, respiratory diseases and diabetes contributed 0.42, 0.62, 0.20, and 0.01 years to life expectancy, respectively. The decline mortality rate of gastric cancer contributed more to the increase of life expectancy compared with lung cancer. The increase in the mortality rate of hypertensive heart disease resulted in a negative contribution. Asthma and diabetes contributed very little to the increase of life expectancy. Conclusions: The increase in the life expectancy of local population in Ji'nan from 2015 to 2020 was mainly attributed to the decline in mortality of four major chronic diseases. It is necessary to pay close attention to the diseases which contributed very little or even had negative contribution to the increase of life expectancy, such as lung cancer, diabetes and hypertensive heart disease.
Subject(s)
Cardiovascular Diseases , Heart Diseases , Hypertension , Lung Neoplasms , Noncommunicable Diseases , Male , Female , Humans , Life ExpectancyABSTRACT
Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA -265.95 ± 1.32 kJ/mol and -124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = -216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= -435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.
Subject(s)
Aedes , Insecticides , Animals , Computational Biology , Humans , Insecticides/pharmacology , Juvenile Hormones , Larva , Piperidines/pharmacology , Plant Extracts/pharmacologyABSTRACT
Skin Cancer (SC) is among the most common type of cancers worldwide. The search for SC therapeutics using molecular modeling strategies as well as considering natural plant-derived products seems to be a promising strategy. The phytochemical Rocaglamide A (Roc-A) and its derivatives rise as an interesting set of reference compounds due to their in vitro cytotoxic activity with SC cell lines. In view of this, we performed a hierarchical virtual screening study considering Roc-A and its derivatives, with the aim to find new chemical entities with potential activity against SC. For this, we selected 15 molecules (Roc-A and 14 derivatives) and initially used them in docking studies to predict their interactions with Checkpoint kinase 1 (Chk1) as a target for SC. This allowed us to compile and use them as a training set to build robust pharmacophore models, validated by Pearson's correlation (p) values and hierarchical cluster analysis (HCA), subsequentially submitted to prospective virtual screening using the Molport® database. Outputted compounds were then selected considering their similarities to Roc-A, followed by analyses of predicted toxicity and pharmacokinetic properties as well as of consensus molecular docking using three software. 10 promising compounds were selected and analyzed in terms of their properties and structural features and, also, considering their previous reports in literature. In this way, the 10 promising virtual hits found in this work may represent potential anti-SC agents and further investigations concerning their biological tests shall be conducted.
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Transport of high-current relativistic electron beams in dense plasmas is of interest in many areas of research. However, so far the mechanism of such beam-plasma interaction is still not well understood due to the appearance of small time- and space-scale effects. Here we identify a new regime of electron beam transport in solid-density plasma, where kinetic effects that develop on small time and space scales play a dominant role. Our three-dimensional particle-in-cell simulations show that in this regime the electron beam can evolve into layered short microelectron bunches when collisions are relatively weak. The phenomenon is attributed to a secondary instability, on the space- and timescales of the electron skin depth (tens of nanometers) and few femtoseconds of strong electrostatic modulation of the microelectron current filaments formed by Weibel-like instability of the original electron beam. Analytical analysis on the amplitude, scale length, and excitation condition of the self-generated electrostatic fields is clearly validated by the simulations.
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Studies in countries with high immunisation coverage suggest that the re-emergence of pertussis may be caused by a decreased duration of protection resulting from the replacement of whole-cell pertussis vaccine (WPV) with the acellular pertussis vaccine (APV). In China, WPV was introduced in 1978. The pertussis vaccination schedule advanced from an all-WPV schedule (1978-2007), to a mixed WPV/APV schedule (2008-2009), then to an all-APV schedule (2010-2016). Increases in the incidence of pertussis have been reported in recent years in Jinan and other cities in China. However, there have been few Chinese-population-based studies focused on the impact of schedule changes. We obtained annual pertussis incidences from 1956 to 2016 from the Jinan Notifiable Conditions Database. We used interrupted time series and segmented regression analyses to assess changes in pertussis incidence at the beginning of each year, and average annual changes during the intervention. Pertussis incidence decreased by 1.11 cases per 100 000 population (P = 0.743) immediately following WPV introduction in 1978 and declined significantly by 1.21 cases per 100 000 population per year (P < 0.0001) between 1978 and 2001. Immediately after APV replaced the fourth dose of WPV in 2008, the second and third doses in 2009, then replaced all four doses in 2010, pertussis incidence declined by 1.98, 1.98 and 1.08 cases per 100 000 population, respectively. However, the results were not statistically significant. There were significant increasing trends in pertussis incidence after APV replacements: 1.63, 1.77 and 1.78 cases/year in 2008-2016, 2009-2016 and 2010-2016, respectively. Our study shows that the impact of an all-WPV schedule may be less than the impacts of the sequential WPV/APV schedules. The short-term impact of APV was better than that of WPV; however, the duration of APV-induced protection was not ideal. The impact and duration of protective immunity resulting from APVs produced in China need further evaluation. Further research on the effectiveness of pertussis vaccination programme in Jinan, China is also necessary.
Subject(s)
Immunization Schedule , Pertussis Vaccine/administration & dosage , Pertussis Vaccine/immunology , Whooping Cough/epidemiology , Whooping Cough/prevention & control , Adolescent , Adult , Child , Child, Preschool , China/epidemiology , Cities/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Interrupted Time Series Analysis , Longitudinal Studies , Male , Middle Aged , Treatment Outcome , Vaccines, Acellular/administration & dosage , Vaccines, Acellular/immunology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Young AdultABSTRACT
Objective: To understand the current status of BMI of the elderly and related factors in longevity areas in China, and provide scientific evidence for the control of BMI level in elderly population. Methods: Data used in this study were obtained from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey. A total of 2 825 elderly in 8 longevity areas in China were surveyed and measured in 2017. The BMI levels of 2 217 elderly aged 65 years and older were calculated and in follow up. The ordered classification logistic regression model was used to analyze the influencd factors for the BMI in the elderly. Results: The BMI of the elderly in 8 longevity areas in China was (22.36±3.87) kg/m(2), and it was (22.76±3.58) kg/m(2) for males and (21.75±3.98) kg/m(2) for females. The BMI levels were normal in 1 165 elderly persons. The prevalence of underweight, overweight and obesity were 15.8%, 24.0% and 7.7%, respectively. Multivariate analysis showed that the main factors affecting the BMI of people under 100- years old were age (65-: OR=2.78, 95%CI: 1.87-4.15; 80-: OR=1.47, 95%CI: 1.00-2.17), smoking status (OR=0.46, 95%CI: 0.32-0.66), annual household income (<30 000 Yuan: OR=1.26, 95%CI: 1.07-1.47; 30 000-70 000 Yuan: OR=1.52, 95%CI: 1.12-1.86), and frequency of tea intake(OR=1.36, 95%CI: 1.01-1.71), while the factor in people aged ≥100 years was gender (OR=3.68, 95%CI: 1.32-10.36). Conclusions: The prevalence of underweight, overweight and obesity were high in the elderly from longevity areas in China. It is necessary to pay attention to the trend of overweight and obesity due to smoking, higher annual household income and regular tea drinking in the elderly men.
Subject(s)
Body Mass Index , Overweight , Aged , Aged, 80 and over , China , Cohort Studies , Female , Humans , Longevity , Male , Risk FactorsABSTRACT
Objective: To investigate the relationship between preoperative evaluation, surgery and prognosis of microvascular decompression (MVD) for the treatment of hemifacial spasm (HFS). Methods: The clinical data of 128 HFS patients treated with MVD in the department of neurosurgery of Taizhou Hospital of Zhejiang Province were retrospectively analyzed. According to the SMC grading system, the patients were divided into general spasm group and severe spasm group, and the clinical characteristics, offending vessel, prognosis and surgical complications of the two groups were compared. Results: In the general spasm group,the age at MVD was (48.6±10.6) years, the disease duration was (4.2±3.3) years;while in the severe spasm group,the age at MVD was (51.8±9.9) years, the disease duration was (8.1±4.5) years;the differences of age and disease duration between the two groups were statistically significant (P<0.05).In the general spasm group, there were 41 cases in which the offending vessel were AICA, 21 cases were PICA, 1 case was VA, 63 cases were single offending vessel, and 7 cases were multiple offending vessels. In the severe spasm group, there were 29 cases in which the offending vessel were AICA, 13 cases were PICA, 2 cases were VA, the total of 44 cases were single offending vessel and 14 cases were multiple offending vessels.There was a significant difference in the proportion of multiple offending vessels in the two groups, and the difference was statistically significant (P<0.05).Patients in the two groups were followed up for 12 to 32 months after surgery, and the difference in effective rate and recurrence rate was not statistically significant (P>0.05).Some kinds of postoperative complications were different between the two groups, the incidence of postoperative delayed facial paralysis was statistically significant (P<0.05), and the other complications were not statistically significant (P>0.05). Conclusion: Compared with the general spasm group, the patients in the severe spasm group were older, with longer disease duration, higher probability of multiple offending vessels and higher incidence of postoperative delayed facial paralysis. Therefore, preoperative SMC grading is helpful for the evaluation and prediction of intraoperative and postoperative conditions, which is worthy of wide clinical application.
Subject(s)
Facial Paralysis , Hemifacial Spasm , Microvascular Decompression Surgery , Adult , Humans , Middle Aged , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
There is a great interest in increasing the levels of production of nanocellulose, either by adjusting production systems or by improving the raw material. Despite all the advantages and applications, nanocellulose still has a high cost compared to common fibers and to reverse this scenario the development of new, cheaper, and more efficient means of production is required. The market trend is to have an increase in the mass production of nanocellulose; there is a great expectation of world trade. In this sense, research in this sector is on the rise, because once the cost is not an obstacle to production, this material will have more and more market. Production of the cellulose fibers is determinant for the production of nanocellulose by a hydrolyzing agent with a reasonable yield. This work presents several aspects of this new material, mainly addressing the enzymatic pathway, presenting the hydrolysis conditions such as pH, biomass concentration, enzymatic loading, temperature, and time. Also, the commonly used characterization methods are presented, as well as aspects of the nanocellulose production market.
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In the present study, the pathogenicity of fowl adenovirus (FAdV) serotype 4 strain HB1501 was systematically determined by using different doses and routes of inoculation in chickens and assessed the immune efficacy induced by fowl adenovirus serotype 4 (FAdV-4) strain SB15 in a vaccination trial. The results revealed that strain HB1501 was highly virulent in chickens, inflicting 30 to 100% mortality when administered by intramuscular and intravenous routes, and its pathogenicity was influenced markedly by the inoculation route. The inactivated oil-emulsion FAdV-4 vaccine derived from strain SB15 completely protected specific pathogen-free chickens against morbidity and mortality following infection with the virulent FAdV-4 strain HB1501. Importantly, no obvious clinical signs or gross lesions were observed and high antibody levels against FAdV were measured in the SB15-vaccinated chickens, indicating the potential of this strain to become an alternative vaccine candidate. This study provides detailed information on the pathogenicity of FAdV-4, which should be of great value to the control of hepatitis-hydropericardium syndrome.
Subject(s)
Adenoviridae Infections/veterinary , Aviadenovirus/immunology , Aviadenovirus/pathogenicity , Chickens/immunology , Poultry Diseases/immunology , Adenoviridae Infections/immunology , Adenoviridae Infections/microbiology , Animals , Poultry Diseases/microbiology , Specific Pathogen-Free Organisms , Vaccination/veterinary , Vaccines, Inactivated/immunology , Viral Vaccines/immunology , VirulenceABSTRACT
Objective: To study the mechanism of interleukin (IL)-17 in mice with non-alcoholic fatty liver disease for promoting M1-type macrophage polarization to exacerbate liver inflammation, and to provide references for the mechanism of NAFLD occurrence and development. Methods: A mouse model of NAFLD was constructed by high-fat diet. Mice were divided into control group, model group, IL-17 group, and anti IL-17 group. Histopathological changes of the liver were observed by HE staining. The serum levels of ALT and AST in peripheral blood of mice was detected by chemical colorimetry. Macrophages labeled with F4/80-PE, CD11C-FITC was designated as M1-type macrophages, those labeled with F4/80-PE, and CD206-APC was designated as M2-type macrophages. The proportion of M1 and M2 macrophages infiltrated into the liver tissues of mice were measured by flow cytometry. CD168 expression level of liver tissues was detected using immunohistochemistry. Protein and mRNA levels of the marker molecules (iNOS, TNF-alpha and IL-6) of M1 macrophages were detected using ELISA and RT-Q PCR. Western blot was used to detect the protein expression of JAK-STAT signal pathway and the expression level of MCP-1. Data were analyzed using one-way ANOVA and t-test. Results: High-fat diet NAFLD mice model was successfully constructed. IL-17 had increased the proportion of M1 macrophages in mice liver tissues and decreased the proportion of M2 macrophages (P < 0.05). The proportion of M1 and M2 macrophages in the liver tissues of normal mice was 7.9% ± 1.1% and 19.2% ± 1.8%. The proportion of M1 and M2 macrophages in the model group was 17.3% ± 2.5% and 15.0% ± 2.1. The proportion of M1 macrophages (33.8% ± 4.2%) in IL-17 group was higher than model group, while the proportion of M2 macrophages (7.8% + 1.0%) in IL-17 group was lower than model group. Protein and mRNA marker levels of M1 macrophage (iNOS, IL-12, TNFα and IL-6) in liver tissues were significantly higher than model group, control group, and anti-IL-17 group (P < 0.05). The expression levels of JAK1, STAT1, MCP-1, and CD168 in mice liver tissues of IL-17 group had increased (P < 0.05). The levels of aspartate and alanine aminotransferases in peripheral blood of mice in IL-17 group were significantly higher than other three groups (P < 0.05). Conclusion: IL-17 can promote M1-type macrophage polarization, and exacerbates the liver inflammatory response to accelerate the progression of NAFLD in mice.