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BACKGROUND: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, ß-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART. METHODS: We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment. RESULTS: ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART. CONCLUSION: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.
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Artemisininas , Hígado , Schistosoma japonicum , Esquistosomiasis Japónica , Animales , Artemisininas/farmacología , Artemisininas/uso terapéutico , Esquistosomiasis Japónica/tratamiento farmacológico , Esquistosomiasis Japónica/prevención & control , Esquistosomiasis Japónica/parasitología , Ratones , Schistosoma japonicum/efectos de los fármacos , Femenino , Masculino , Hígado/parasitología , Hígado/patología , Hígado/efectos de los fármacos , Citocinas/metabolismo , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Strain engineering has been widely used to optimize platinum-based oxygen reduction reaction (ORR) catalysts for proton exchange membrane fuel cells (PEMFCs). PtM3 (M is base metals), a well-known high-compressive-strain intermetallic alloy, shows promise as a low platinum ORR catalyst due to high intrinsic activity. However, during the alloying of Pt with a threefold amount of M, a notable phase separation between Pt and M may occur, with M particles rapidly sintering while Pt particles grow slowly, posing a challenge in achieving a well-defined PtM3 intermetallic alloy. Here, an entropy-driven Ostwald ripening reversal phenomenon is discovered that enables the synthesis of small-sized Pt(FeCoNiCu)3 intermetallic ORR catalysts. High entropy promotes the thermodynamic driving force for the alloying Pt with M, which triggers the Ostwald ripening reversal of sintered FeCoNiCu particles and facilitates the formation of uniform Pt(FeCoNiCu)3 intermetallic catalysts. The prepared Pt(FeCoNiCu)3 catalysts exhibit a high specific activity of 3.82 mA cm-2, along with a power density of ≈1.3 W cm-2 at 0.67 V and 94 °C with a cathode Pt loading of 0.1 mg cm-2 in H2-air fuel cell.
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The fine-tuning of the geometric and electronic structures of active sites plays a crucial role in catalysis. However, the intricate entanglement between the two aspects results in a lack of interpretable design for active sites, posing a challenge in developing high-performance catalysts. Here, we find that surface reconstruction induced by phase transition in intermetallic alloys enables synergistic geometric and electronic structure modulation, creating a desired active site microenvironment for propane dehydrogenation. The resulting electron-rich four-coordinate Rh1 site in the RhGe0.5Ga0.5 intermetallic alloy can accelerate the desorption of propylene and suppress the side reaction and thus exhibits a propylene selectivity of â¼98% with a low deactivation constant of 0.002 h-1 under propane dehydrogenation at 550 °C. Furthermore, we design a computational workflow to validate the rationality of the microenvironment modulation induced by the phase transition in an intermetallic alloy.
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Escherichia coli Nissle 1917 (EcN) is an important chassis strain widely used for the development of live biotherapeutic products (LBPs). EcN strain naturally harbors two cryptic plasmids with unknown function. During the development of LBPs using EcN strain, the cryptic plasmids were cured usually to avoid plasmid incompatibility or alleviate metabolic burdens associated with these cryptic plasmids. While the cryptic plasmids curing in EcN may appear to be a routine procedure, the comprehensive impact of cryptic plasmids curing on the EcN strain remains incompletely understood. In the present study, the effects of cryptic plasmids curing on EcN were investigated using transcriptome sequencing. The results revealed that only a small number of genes showed significant changes in mRNA levels after cryptic plasmid curing (4 upregulated and 6 downregulated genes), primarily involved in amino acid metabolism. Furthermore, the flu gene showed the most significant different expression, encoding Antigen 43 (Ag43) protein, a Cah family adhesin. Mass spectrometry analysis further confirmed the significant increase in Ag43 expression. Ag43 is commonly present in Escherichia coli and mediates the bacterial autoaggregation. However, despite the upregulation of Ag43 expression, no Ag43-mediated cell self-sedimentation was observed in the cured EcN strain. These findings contribute to making informed decisions regarding the curing of the cryptic plasmids when Escherichia coli Nissle 1917 is used as the chassis strain.
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The catalytic performance of single-atom catalysts was strictly limited by isolated single-atom sites. Fabricating high-density single atoms to realize the synergetic interaction in neighbouring single atoms could optimize the adsorption behaviors of reaction intermediates, which exhibited great potential to break performance limitations and deepen mechanistic understanding of electrocatalysis. However, the catalytic behavior governed by neighbouring single atoms is particularly elusive and has yet to be understood. Herein, we revealed that the synergetic interaction in neighbouring single atoms contributes to superior performance for oxygen evolution relative to isolated Ir single atoms. Neighbouring single atoms was achieved by fabricating high-density single atoms to narrow the distance between single atoms. Electrochemical measurements demonstrated that the Nei-Ir1/CoGaOOH with neighbouring Ir single atoms exhibited a low overpotential of 170â mV at a current density of 10â mA cm-2, and long-durable stability over 2000â h for oxygen evolution. Mechanistic studies revealed that neighbouring single atoms synergetic stabilized the *OOH intermediates via extra hydrogen bonding interactions, thus significantly reducing the reaction energy barriers, as compared to isolated Ir single atoms. The discovery of the synergetic interaction in neighbouring single atoms could offer guidance for the development of efficient electrocatalysts, thus accelerating the world's transition to sustainable energy.
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Developing efficient and economical electrocatalysts for acidic oxygen evolution reaction (OER) is essential for proton exchange membrane water electrolyzers (PEMWE). Cobalt oxides are considered promising non-precious OER catalysts due to their high activities. However, the severe dissolution of Co atoms in acid media leads to the collapse of crystal structure, which impedes their application in PEMWE. Here, we report that introducing acid-resistant Ir single atoms into the lattice of spinel cobalt oxides can significantly suppress the Co dissolution and keep them highly stable during the acidic OER process. Combining theoretical and experimental studies, we reveal that the stabilizing effect induced by Ir heteroatoms exhibits a strong dependence on the distance of adjacent Ir single atoms, where the OER stability of cobalt oxides continuously improves with decreasing the distance. When the distance reduces to about 0.6 nm, the spinel cobalt oxides present no obvious degradation over a 60-h stability test for acidic OER, suggesting potential for practical applications.
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Carbon supported PtCo intermetallic alloys are known to be one of the most promising candidates as low-platinum oxygen reduction reaction electrocatalysts for proton-exchange-membrane fuel cells. Nevertheless, the intrinsic trade-off between particle size and ordering degree of PtCo makes it challenging to simultaneously achieve a high specific activity and a large active surface area. Here, by machine-learning-accelerated screenings from the immense configuration space, we are able to statistically quantify the impact of chemical ordering on thermodynamic stability. We find that introducing of Cu/Ni into PtCo can provide additional stabilization energy by inducing Co-Cu/Ni disorder, thus facilitating the ordering process and achieveing an improved tradeoff between specific activity and active surface area. Guided by the theoretical prediction, the small sized and highly ordered ternary Pt2CoCu and Pt2CoNi catalysts are experimentally prepared, showing a large electrochemically active surface area of ~90 m2 gPtâ1 and a high specific activity of ~3.5 mA cmâ2.
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Photoreceptor cell death, primarily through apoptosis, related to retinal disorders like retinitis pigmentosa (RP), would result in vision loss. The pathological processes and crucial mutant conditions preceding photoreceptor cell demise are not well understood. This study aims to conduct an in-depth examination of early-stage changes in the widely utilized Pde6brd1/rd1 (rd1) mouse model, which has Pde6b gene mutations representing autosomal recessive RP disorder. We investigated the morphology and ultrastructure of retinal cells, including second-order neurons, during the initial phase of disease progression. Our findings revealed that mitochondrial alterations in rod photoreceptors were present as a predeath mutant state as early as postnatal day 3 (P3). The bipolar and horizontal cells from the rd1 mouse retina exhibited significant morphological changes in response to loss of photoreceptor cells, indicating that second-order neurons rely on these cells for their structures. Subsequent oral administration of idebenone, a mitochondria-protective agent, enhanced retinal function and promoted both photoreceptor cell survival and inner retinal second-order synaptogenesis in rd1 mice at P14. Our findings offer a mechanistic framework, suggesting that mitochondrial damage acts as an early driver for photoreceptor cell death in retinal degeneration.
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Distrofias Retinianas , Retinitis Pigmentosa , Animales , Ratones , Ubiquinona , Retina , Modelos Animales de Enfermedad , Células Fotorreceptoras Retinianas BastonesRESUMEN
Exploring economical, efficient, and stable electrocatalysts for the seawater hydrogen evolution reaction (HER) is highly desirable but is challenging. In this study, a Mo cation doped Ni0.85Se/MoSe2 heterostructural electrocatalyst, Mox-Ni0.85Se/MoSe2, was successfully prepared by simultaneously doping Mo cations into the Ni0.85Se lattice (Mox-Ni0.85Se) and growing atomic MoSe2 nanosheets epitaxially at the edge of the Mox-Ni0.85Se. Such an Mox-Ni0.85Se/MoSe2 catalyst requires only 110 mV to drive current densities of 10 mA cm-2 in alkaline simulated seawater, and shows almost no obvious degradation after 80 h at 20 mA cm-2. The experimental results, combined with the density functional theory calculations, reveal that the Mox-Ni0.85Se/MoSe2 heterostructure will generate an interfacial electric field to facilitate the electron transfer, thus reducing the water dissociation barrier. Significantly, the heteroatomic Mo-doping in the Ni0.85Se can regulate the local electronic configuration of the Mox-Ni0.85Se/MoSe2 heterostructure catalyst by altering the coordination environment and orbital hybridization, thereby weakening the bonding interaction between the Cl and Se/Mo. This synergistic effect for the Mox-Ni0.85Se/MoSe2 heterostructure will simultaneously enhance the catalytic activity and durability, without poisoning or corrosion of the chloride ions.
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Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathways are required to be tightly controlled to initiate host innate immune responses. Fish mitochondrial antiviral signaling (mavs) is a key determinant in the RLR pathway, and its ubiquitination is associated with mavs activation. Here, we identified the zebrafish E3 ubiquitin ligase Speckle-type BTB-POZ protein (spop) negatively regulates mavs-mediated the type I interferon (IFN) responses. Consistently, overexpression of zebrafish spop repressed the activity of IFN promoter and reduced host ifn transcription, whereas knockdown spop by small interfering RNA (siRNA) transfection had the opposite effects. Accordingly, overexpression of spop dampened the cellular antiviral responses triggered by spring viremia of carp virus (SVCV). A functional domain assay revealed that the N-terminal substrate-binding MATH domain regions of spop were necessary for IFN suppression. Further assays indicated that spop interacts with mavs through the C-terminal transmembrane (TM) domain of mavs. Moreover, zebrafish spop selectively promotes K48-linked polyubiquitination and degradation of mavs through the lysosomal pathway to suppress IFN expression. Our findings unearth a post-translational mechanism by which mavs is regulated and reveal a role for spop in inhibiting antiviral innate responses.
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Transducción de Señal , Pez Cebra , Animales , Ubiquitinación , Inmunidad Innata , AntiviralesRESUMEN
AIMS: Based on our previous research on the specific miRNAs identified from Gastrodia elata, we selected Gas-miR2-3p to investigate its effects on neuroinflammation via in vitro and in vivo experiments. RESULTS: RT-qPCR analysis indicated that G. elata specific Gas-miR2-3p was detected in all murine tissues post-oral administration, suggesting their potential as orally bioavailable miRNA. The analysis of RT-qPCR, Western blotting and ELISA assays consistently demonstrate that the expression of inflammatory factors as TNF-α, IL-6, IL-1ß was decreased and the expression levels of p-p65 and p-IκBα were downregulated after the action of Gas-miR2-3p in both cell and animal experiments. CONCLUSION: Gas-miR2-3p can attenuate neuroinflammation by regulating the inflammation factors and suppressing the activation of the NF-κB signaling pathway. Our findings indicate that G. elata miRNAs, as novel active components, perform a modulatory role in the NF-κB signaling pathway associated with neuroinflammation in a cross-species way.
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INTRODUCTION: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. METHODS: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. RESULTS: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. CONCLUSIONS: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings.
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Ventrículos Cardíacos , Fallo Renal Crónico , Humanos , Ventrículos Cardíacos/diagnóstico por imagen , Diálisis Renal , Volumen Sistólico , Función Ventricular Izquierda , Estudios Transversales , Fallo Renal Crónico/terapiaRESUMEN
BACKGROUND: To develop machine learning models for objectively evaluating visual acuity (VA) based on pattern-reversal visual evoked potentials (PRVEPs) and other related visual parameters. METHODS: Twenty-four volunteers were recruited and forty-eight eyes were divided into four groups of 1.0, 0.8, 0.6, and 0.4 (decimal vision). The relationship between VA, peak time, or amplitude of P100 recorded at 5.7°, 2.6°, 1°, 34', 15', and 7' check sizes were analyzed using repeated-measures analysis of variance. Correlations between VA and P100, contrast sensitivity (CS), refractive error, wavefront aberrations, and visual field were analyzed by rank correlation. Based on meaningful P100 peak time, P100 amplitude, and other related visual parameters, four machine learning algorithms and an ensemble classification algorithm were used to construct objective assessment models for VA. Receiver operating characteristic (ROC) curves were used to compare the efficacy of different models by repeated sampling comparisons and ten-fold cross-validation. RESULTS: The main effects of P100 peak time and amplitude between different VA and check sizes were statistically significant (all P < 0.05). Except amplitude at 2.6° and 5.7°, VA was negatively correlated with peak time and positively correlated with amplitude. The peak time initially shortened with increasing check size and gradually lengthened after the minimum value was reached at 1°. At the 1° check size, there were statistically significant differences when comparing the peak times between the vision groups with each other (all P < 0.05), and the amplitudes of the vision reduction groups were significantly lower than that of the 1.0 vision group (all P < 0.01). The correlations between peak time, amplitude, and visual acuity were all highest at 1° (rs = - 0.740, 0.438). VA positively correlated with CS and spherical equivalent (all P < 0.001). There was a negative correlation between VA and coma aberrations (P < 0.05). For different binarization classifications of VA, the classifier models with the best assessment efficacy all had the mean area under the ROC curves (AUC) above 0.95 for 500 replicate samples and above 0.84 for ten-fold cross-validation. CONCLUSIONS: Machine learning models established by meaning visual parameters related to visual acuity can assist in the objective evaluation of VA.
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Potenciales Evocados Visuales , Visión Ocular , Humanos , Estudios de Factibilidad , Agudeza Visual , AlgoritmosRESUMEN
BACKGROUND: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice. OBJECTIVE: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD: A prospective screening study at the DM complication screening centre was performed. RESULTS: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%. CONCLUSION: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.
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Fibrilación Atrial , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Accidente Cerebrovascular , Disfunción Ventricular Izquierda , Humanos , Masculino , Persona de Mediana Edad , Anciano , Volumen Sistólico , Función Ventricular Izquierda , Estudios Prospectivos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/etiología , Biomarcadores , Accidente Cerebrovascular/etiología , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnósticoRESUMEN
Integrating single atoms and clusters into one system is a novel strategy to achieve desired catalytic performances. Compared with homogeneous single-atom cluster catalysts, heterogeneous ones combine the merits of different species and therefore show greater potential. However, it is still challenging to construct single-atom cluster systems of heterogeneous species, and the underlying mechanism for activity improvement remains unclear. In this work, we developed a heterogeneous single-atom cluster catalyst (ConIr1/N-C) for efficient oxygen evolution. The Ir single atoms worked in synergy with the Co clusters at a distance of about 8 Å, which optimized the configuration of the key intermediates. Consequently, the oxygen evolution activity was significantly improved on ConIr1/N-C relative to the Co cluster catalyst (Con/N-C), exhibiting an overpotential lower by 107 mV than that of Con/N-C at 10 mA cm-2 and a turnover frequency 50.9 times as much as that of Con/N-C at an overpotential of 300 mV.
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The cycloaddition of CO2 with epoxides towards cyclic carbonates provides a promising pathway for CO2 utilization. Given the crucial role of epoxide ring opening in determining the reaction rate, designing catalysts with rich active sites for boosting epoxide adsorption and C-O bond cleavage is necessary for gaining efficient cyclic carbonate generation. Herein, by taking two-dimensional FeOCl as a model, we propose the construction of electron-donor and -acceptor units within a confined region via vacancy-cluster engineering to boost epoxide ring opening. By combing theoretical simulations and in situ diffuse reflectance infrared Fourier-transform spectroscopy, we show that the introduction of Fe-Cl vacancy clusters can activate the inert halogen-terminated surface and provide reactive sites containing electron-donor and -acceptor units, leading to strengthened epoxide adsorption and promoted C-O bond cleavage. Benefiting from these, FeOCl nanosheets with Fe-Cl vacancy clusters exhibit enhanced cyclic carbonate generation from CO2 cycloaddition with epoxides.
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Sarcopenia, characterized by degenerative and systemic loss of skeletal muscle mass and function, is a multifactorial syndrome commonly observed in individuals with cancer. Additionally, it represents a poor nutritional status and indicates possible presence of cancer cachexia. Recently, with the extensive application of cancer immunotherapy, the effects of sarcopenia/cachexia on cancer immunotherapy, have gained attention. The aim of this review was to summarize the influence of low muscle mass (sarcopenia/cachexia) on the response and immune-related adverse events to immunotherapy from the latest literature. It was revealed that low muscle mass (sarcopenia/cachexia) has detrimental effects on cancer immunotherapy in most cases, although there were results that were not consistent with this finding. This review also discussed potential causes of the paradox, such as different measure methods, research types, muscle indicators, time point, and cancer type. Mechanically, chronic inflammation, immune cells, and microbiota may be critically involved in regulating the efficacy of immunotherapy under the condition of low muscle mass (sarcopenia/cachexia). Thus, nutritional interventions will likely be promising ways for individuals with cancer to increase the efficacy of immunotherapy in the future, for low muscle mass (sarcopenia/cachexia) is an important prognostic factor for cancer immunotherapy.
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Microbiota , Neoplasias , Sarcopenia , Humanos , Sarcopenia/terapia , Sarcopenia/complicaciones , Caquexia/etiología , Caquexia/terapia , Caquexia/patología , Músculo Esquelético , Inflamación/complicaciones , Neoplasias/complicaciones , Neoplasias/terapia , Neoplasias/patología , Inmunoterapia/efectos adversosRESUMEN
To compare the potential influences of blind insertion and up-down optimized glottic exposure manoeuvre on the oropharyngeal leak pressure (OPLP) in using SaCoVLM™ video laryngeal mask (VLM) among patients undergoing general anesthesia. A randomized self-control study controlled was conducted to investigate the effect of two insertion techniques on OPLP. A total of 60 patients (male or female, 18-78 years, BMI 18.0-30.0 kg m-2 and ASA I-II) receiving selective surgery under general anesthesia were randomly recruited. After induction of anesthesia, the SaCoVLM™ was inserted by blind insertion manoeuvre. The glottic exposure grading(V1) of the SaCoVLM™ visual laryngeal mask and the OPLP(P1) were recorded. And the glottic exposure grading(V2) and OPLP(P2) of SaCoVLM™ were recorded again when the glottic exposure grading was optimal. The glottis exposure grading and OPLP were compared before and after different insertion manoeuver. The glottic exposure grading (V2) obtained by using up-down optimized glottic exposure manoeuvre was better than that obtained by using blind insertion manoeuvre (V1)(P < 0.001). The OPLP was significantly lower in the blind insertion manoeuvre (P1) than in the up-down optimized glottic exposure manoeuvre (P2) (32.4 ± 5.0 cmH2O vs. 36.3 ± 5.2 cmH2O, P < 0.001). In using SaCoVLM™, higher OPLP and better glottic exposure grading were achieved through up-down optimized glottic exposure manoeuvre, protecting the airway while real-time monitoring of conditions around the glottis, which significantly improves airway safety. Our results suggests that up-down optimized glottic exposure manoeuver may be a useful technique for SaCoVLM™ insertion.Trial registration: ChiCTR, ChiCTR2000028802. Registered 4 January 2020, http://www.chictr.org.cn/ChiCTR2000028802.
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Anestesiología , Máscaras Laríngeas , Humanos , Masculino , Femenino , Anestesia General/métodos , Intubación Intratraqueal/métodos , GlotisRESUMEN
AIM: To explore the mechanism of fructus lycii in treating dry eye based on network pharmacology and experimental verification.METHODS: Taking “fructus lycii” as key words, the active ingredients and target of fructus lycii were searched by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Gene targets related to dry eye(DE)were searched by GeneCards and OMIM databases. The target genes of fructus lycii and DE were imported into Venn software to obtain the intersection target map of them. After that, the data were imported into the String database to obtain the PPI protein-protein interaction network diagram. Using Cytoscape3.7.2 software, the PPI protein-protein interaction network diagram was constructed for active ingredients, target sites and related diseases of fructus lycii. The Bioconductor platform and R language were used for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis. And the key targets in the pathogenesis of DE were verified by experiments.RESULTS: Through TCMSP, 45 types of effective chemical components of fructus lycii, 174 target genes corresponding to active components and 131 common target genes with DE were screenedout. In accordance with the network topology of “drug-composition-disease-target”, 27 main effective components of fructus lycii were found in the treatment of DE. The PPI network was analyzed according to the high degree value, which is the key targets of fructus lycii for DE treatment, mainly including AKT1, VEGFA, CASP3, IL1B, JUN, PTGS2, CXCL8, etc. According to GO enrichment analysis, 166 biological functions and processes of fructus lycii for DE treatment were obtained. KEGG enrichment analysis showed that 31 signaling pathways were involved. Additionally, experimental verification displayed that the protein expressions of AKT1, interleukin-6(IL-6), tumor necrosis factor(TNF-α)and IL-17 in conjunctiva tissue of the DE model group were significantly increased.CONCLUSIONS: Through network pharmacology, this study confirmed that the treatment of DE by fructus lycii is a complex process involving multi-components, multi-targets and multi-pathways, and that the treatment of DE by fructus lycii is mainly regulated by anti-inflammatory and apoptosis-related molecules.