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Modal-free optimization algorithms do not require specific mathematical models, and they, along with their other benefits, have great application potential in adaptive optics. In this study, two different algorithms, the single-dimensional perturbation descent algorithm (SDPD) and the second-order stochastic parallel gradient descent algorithm (2SPGD), are proposed for wavefront sensorless adaptive optics, and a theoretical analysis of the algorithms' convergence rates is presented. The results demonstrate that the single-dimensional perturbation descent algorithm outperforms the stochastic parallel gradient descent (SPGD) and 2SPGD algorithms in terms of convergence speed. Then, a 32-unit deformable mirror is constructed as the wavefront corrector, and the SPGD, single-dimensional perturbation descent, and 2SPSA algorithms are used in an adaptive optics numerical simulation model of the wavefront controller. Similarly, a 39-unit deformable mirror is constructed as the wavefront controller, and the SPGD and single-dimensional perturbation descent algorithms are used in an adaptive optics experimental verification device of the wavefront controller. The outcomes demonstrate that the convergence speed of the algorithm developed in this paper is more than twice as fast as that of the SPGD and 2SPGD algorithms, and the convergence accuracy of the algorithm is 4% better than that of the SPGD algorithm.
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Primary microcephaly (PMCPH) is a rare autosomal recessive neurodevelopmental disorder with a global prevalence of PMCPH ranging from 0.0013% to 0.15%. Recently, a homozygous missense mutation in YIPF5 (p.W218R) was identified as a causative mutation of severe microcephaly. In this study, we constructed a rabbit PMCPH model harboring YIPF5 (p.W218R) mutation using SpRY-ABEmax mediated base substitution, which precisely recapitulated the typical symptoms of human PMCPH. Compared with wild-type controls, the mutant rabbits exhibited stunted growth, reduced head circumference, altered motor ability, and decreased survival rates. Further investigation based on model rabbit elucidated that altered YIPF5 function in cortical neurons could lead to endoplasmic reticulum stress and neurodevelopmental disorders, interference of the generation of apical progenitors (APs), the first generation of progenitors in the developing cortex. Furthermore, these YIPF5-mutant rabbits support a correlation between unfolded protein responses (UPR) induced by endoplasmic reticulum stress (ERS), and the development of PMCPH, thus providing a new perspective on the role of YIPF5 in human brain development and a theoretical basis for the differential diagnosis and clinical treatment of PMCPH. To our knowledge, this is the first gene-edited rabbit model of PMCPH. The model better mimics the clinical features of human microcephaly than the traditional mouse models. Hence, it provides great potential for understanding the pathogenesis and developing novel diagnostic and therapeutic approaches for PMCPH.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint damage and even permanent disability, seriously affecting patients' quality of life. At present, the complete cure for RA is not achievable, only to relieve the symptoms to reduce the pain of patients. Factors such as environment, genes, and sex can induce RA. Presently, non-steroidal anti-inflammatory drugs, DRMADs, and glucocorticoids are commonly used in treating RA. In recent years, some biological agents have also been applied in clinical practice, but most have side effects. Therefore, finding new mechanisms and targets for treating RA is necessary. This review summarizes some potential targets discovered from the perspective of epigenetics and RA mechanisms.
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Artritis Reumatoide , Enfermedades Autoinmunes , Humanos , Calidad de Vida , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Enfermedades Autoinmunes/genética , Epigénesis Genética , Transducción de SeñalRESUMEN
Background: Single nucleotide polymorphisms (SNPs) interfere with the function of certain genes and thus may influence the probability of skin cancer. The correlation between SNPs and skin cancer (SC) lacks statistical power, however. Therefore, the purpose of this study was to identify the gene polymorphisms involved in skin cancer susceptibility using network meta-analysis and to determine the relationship between SNPs and SC risk. Methods: PubMed, Embase, and Web of Science were searched for articles including "SNP" and different types of SC as keywords between January 2005 and May 2022. The Newcastle-Ottawa Scale was used to assess bias judgments. The odds ratio (ORs) and their 95% confidence intervals (CIs) were determined to estimate heterogeneity within and between studies. Meta-analysis and network meta-analysis were carried out to identify the SNPs associated with SC. The P-score of each SNP was compared to obtain the rank of probability. Subgroup analyses were performed by cancer type. Results: A total of 275 SNPs from 59 studies were included in the study. Two subgroup SNP networks using the allele model and dominant model were analyzed. The alternative alleles of rs2228570 (FokI) and rs13181 (ERCC2) were the first-ranking SNPs in both subgroups one and two of the allele model, respectively. The homozygous dominant genotype and heterozygous genotype of rs475007 in subgroup one and the homozygous recessive genotype of rs238406 in subgroup two were most likely to be associated with skin cancer based on the dominant model. Conclusions: According to the allele model, SNPs FokI rs2228570 and ERCC2 rs13181 and, according to the dominant model, SNPs MMP1 rs475007 and ERCC2 rs238406 are closely linked to SC risk.
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Introduction: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals. Methods: A total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis. Results: At 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron. Discussion: This study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges. Clinical trial registration: https://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.
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COVID-19 , Infecciones por VIH , Humanos , VIH , Vacunas contra la COVID-19 , Seroconversión , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos Neutralizantes , VacunaciónRESUMEN
BACKGROUND: The ongoing benefits of coronavirus disease 2019 (COVID-19) nonpharmaceutical interventions (NPIs) for respiratory infectious diseases in China are still unclear. We aimed to explore the changes in seven respiratory infectious diseases before, during, and after COVID-19 in China from 2010 to 2021. METHODS: The monthly case numbers of seven respiratory infectious diseases were extracted to construct autoregressive integrated moving average (ARIMA) models. Eight indicators of NPIs were chosen from the COVID-19 Government Response Tracker system. The monthly case numbers of the respiratory diseases and the eight indicators were used to establish the Multivariable generalized linear model (GLM) to calculate the incidence rate ratios (IRRs). RESULTS: Compared with the year 2019, the percentage changes in 2020 and 2021 were all below 100% ranging from 3.81 to 84.71%. Pertussis and Scarlet fever started to increase in 2021 compared with 2020, with a percentage change of 183.46 and 171.49%. The ARIMA model showed a good fit, and the predicted data fitted well with the actual data from 2010 to 2019, but the predicted data was bigger than the actual number in 2020 and 2021. All eight indicators could negatively affect the incidence of respiratory diseases. The seven respiratory diseases were significantly reduced during the COVID-19 pandemic in 2020 and 2021 compared with 2019, with significant estimated IRRs ranging from 0.06 to 0.85. In the GLM using data for the year 2020 and 2021, the IRRs were not significant after adjusting for the eight indicators in multivariate analysis. CONCLUSION: Our study demonstrated the incidence of the seven respiratory diseases decreased rapidly during the COVID-19 pandemic in 2020 and 2021. At the end of 2021, we did see a rising trend for the seven respiratory diseases compared to the year 2020 when the NPIs relaxed in China, but the rising trend was not significant after adjusting for the NPIs indicators. Our study showed that NPIs have an effect on respiratory diseases, but Relaxation of NPIs might lead to the resurgence of respiratory diseases.
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COVID-19 , Trastornos Respiratorios , Enfermedades Respiratorias , Humanos , Pandemias , COVID-19/epidemiología , Enfermedades Respiratorias/epidemiología , China/epidemiologíaRESUMEN
Spiders are important models for evolutionary studies of web building, sexual selection and adaptive radiation. The recent development of probes for UCE (ultra-conserved element)-based phylogenomic studies has shed light on the phylogeny and evolution of spiders. However, the two available UCE probe sets for spider phylogenomics (Spider and Arachnida probe sets) have relatively low capture efficiency within spiders, and are not optimized for the retrolateral tibial apophysis (RTA) clade, a hyperdiverse lineage that is key to understanding the evolution and diversification of spiders. In this study, we sequenced 15 genomes of species in the RTA clade, and using eight reference genomes, we developed a new UCE probe set (41 845 probes targeting 3802 loci, labelled as the RTA probe set). The performance of the RTA probes in resolving the phylogeny of the RTA clade was compared with the Spider and Arachnida probes through an in-silico test on 19 genomes. We also tested the new probe set empirically on 28 spider species of major spider lineages. The results showed that the RTA probes recovered twice and four times as many loci as the other two probe sets, and the phylogeny from the RTA UCEs provided higher support for certain relationships. This newly developed UCE probe set shows higher capture efficiency empirically and is particularly advantageous for phylogenomic and evolutionary studies of RTA clade and jumping spiders.
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Arácnidos , Arañas , Animales , Filogenia , Arañas/genética , Arácnidos/genética , Genoma , TibiaRESUMEN
Coronavirus disease 2019 (COVID-19) patients with liver dysfunction (LD) have a higher chance of developing severe and critical disease. The routine hepatic biochemical parameters ALT, AST, GGT, and TBIL have limitations in reflecting COVID-19-related LD. In this study, we performed proteomic analysis on 397 serum samples from 98 COVID-19 patients to identify new biomarkers for LD. We then established 19 simple machine learning models using proteomic measurements and clinical variables to predict LD in a development cohort of 74 COVID-19 patients with normal hepatic biochemical parameters. The model based on the biomarker ANGL3 and sex (AS) exhibited the best discrimination (time-dependent AUCs: 0.60-0.80), calibration, and net benefit in the development cohort, and the accuracy of this model was 69.0-73.8% in an independent cohort. The AS model exhibits great potential in supporting optimization of therapeutic strategies for COVID-19 patients with a high risk of LD. This model is publicly available at https://xixihospital-liufang.shinyapps.io/DynNomapp/.
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COVID-19 , Hepatopatías , Humanos , Proteómica , Aprendizaje AutomáticoRESUMEN
The application of livestock manure is the leading cause of antibiotic and heavy metal pollution in agricultural soil. However, the effects of oxytetracycline (OTC) and lead (Pb) pollution in the single or combined form on antibiotic resistance genes (ARGs) in the soil need to be further studied. This study was planned to investigate the effects of OTC and Pb application on ARGs, mobile genetic elements (MGEs), and bacterial abundance in the soil. The relative abundance of ARGs and MGEs increased by 0.31-fold and 0.03-fold after the addition of 80 mg kg-1 Pb to the soil, and by 0.49-fold and 0.03-fold after the addition of 160 mg kg-1 Pb. In addition, under the premise of the existence of OTC, the inhibitory effect of a low concentration of Pb on ARG is stronger than that of a high concentration of Pb, resulting in a lower abundance of ARGs. The abundance of ARGs and MGEs increased by 0.11-fold and 0.17-fold after the addition of OTC (30 mg kg-1) to the soil at a Pb concentration of 80 mg kg-1 and by 0.18-fold and 0.04-fold at a Pb concentration of 160 mg kg-1. The addition of OTC and Pb in the soil also decreased the many bacterial communities such as Bacteroidetes, Proteobacteria, Acidobacteria, and Firmicutes. Redundancy analysis (RDA) showed that organic matter content and pH were positively correlated with the abundance of ARGs and MGEs. At the same time, electrical conductivity (EC) had a negative correlation with the abundance of ARGs and MGEs in the soil. Intl1 was significantly associated with tetB, sul1, tetQ, sul2, and sul3. Network analysis illustrated that Actinobacteria, Bacteroidetes, and Proteobacteria were the main host bacteria causing changes in the abundance of ARGs and MGEs, and they were also predominant phylum in the culture environment. This conclusion can provide a reference for the related research of ARGs in soil.
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Microbiota , Oxitetraciclina , Oxitetraciclina/farmacología , Suelo/química , Antibacterianos/farmacología , Antibacterianos/análisis , Genes Bacterianos , Plomo/análisis , Farmacorresistencia Microbiana/genética , Estiércol/microbiología , Bacterias/genética , Microbiología del Suelo , Secuencias Repetitivas EsparcidasRESUMEN
Cardiac fibrosis is a common cause of most cardiovascular diseases. Leonurine, an alkaloid from Herba leonuri, had been indicated to treat cardiovascular diseases due to its cardioprotective effects. Recently, pyroptosis, a programmed form of cell death that releases inflammatory factors, has been shown to play an important role in cardiovascular diseases, especially cardiac fibrosis. This study examined the novel mechanism by which leonurine protects against cardiac fibrosis. In rats with isoprenaline-induced cardiac fibrosis, leonurine inhibited the expression of proteins related to pyroptosis and improved cardiac fibrosis. In vitro, leonurine inhibited the expression of proteins related to pyroptosis and fibrosis. Additionally, leonurine regulated the TGF-ß/Smad2 signalling pathway and inhibited pyroptosis to protect cardiomyocytes and improve cardiac fibrosis. Therefore, leonurine might improve cardiac fibrosis induced by isoprenaline by inhibiting pyroptosis via the TGF-ß/Smad2 signalling pathway.
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Enfermedades Cardiovasculares , Miocitos Cardíacos , Animales , Ratas , Enfermedades Cardiovasculares/patología , Fibrosis , Isoproterenol/farmacología , Miocitos Cardíacos/metabolismo , Piroptosis , Factor de Crecimiento Transformador beta/metabolismo , Transducción de SeñalRESUMEN
Natural products, those molecules derived from nature, have been used by humans for thousands of years to treat ailments and diseases. More recently, these compounds have inspired chemists to use natural products as structural templates in the development of new drug molecules. One such compound is leonurine, a molecule isolated and characterized in the tissues of Herb leonuri. This molecule has received attention from scientists in recent years due to its potent anti-oxidant, anti-apoptotic, and anti-inflammatory properties. More recently researchers have shown leonurine to be useful in the treatment of cardiovascular and nervous system diseases. Like other natural products such as paclitaxel and artemisinin, the historical development of leonurine as a therapeutic is very interesting. Therefore, this review provided an overview of natural product discovery, through to the development of a potential new drug. Content will summarize known plant sources, the pathway used in the synthesis of leonurine, and descriptions of leonurine's pharmacological properties in mammalian systems.
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Tumor-derived extracellular vesicles (EVs) are key immune regulators of the tumor microenvironment. They reshape the immune microenvironment and prevent antitumor immune responses via their immunosuppressive cargo, thereby determining cancer responsiveness to treatment. In the immune microenvironment of melanoma, tumor-derived EVs influence tumor progression by regulating innate and adaptive immune responses. Tumor-derived EV-based therapy is a cutting-edge and promising strategy for inhibiting melanoma progression and enhancing antitumor immunity. This review aimed to summarize the regulatory roles of EVs in the immune responses and immunotherapy of patients with melanoma. This paper provided insights into future exploration directions and potential clinical strategies targeting EVs for melanoma treatment.
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Vesículas Extracelulares , Melanoma , Humanos , Vesículas Extracelulares/patología , Melanoma/patología , Inmunoterapia , Microambiente Tumoral , InmunidadRESUMEN
BACKGROUND: Long noncoding RNAs (lncRNAs) are closely associated with the initiation, progression, metastasis, and recurrence of hepatocellular carcinoma (HCC). They could therefore serve as markers for the early diagnosis and for the prognosis of HCC patients. METHODS: This was an observational prospective cohort study. A total of 101 participants were included, comprising patients with HCC (n = 61), liver cirrhosis (LC) (n = 20), or healthy controls (HC) (n = 20). The baseline characteristics of participants in each group were compared. Serum levels of the lncRNAs HOTAIR, BRM and ICR were determined in each group by reverse transcription and quantitative real-time polymerase chain reaction (qRT-PCR). Correlations between the serum levels of the three lncRNAs and multiple clinical parameters were analysed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic potential for HCC of each lncRNA individually, or in combination with AFP. Multivariate Cox regression analysis was used to evaluate the accuracy of these lncRNAs for predicting the outcome and survival of HCC patients. RESULTS: The serum levels of HOTAIR, BRM and ICR were significantly higher in HCC patients compared to LC patients and healthy subjects. The HOTAIR level was positively correlated to tumour-node metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) stage, extrahepatic metastasis, vascular invasion, portal vein tumour thrombus (PVTT), and tumour size. The BRM level was positively associated with TNM stage, BCLC stage, vascular invasion, PVTT, and tumour size, while the ICR level was positively correlated with PVTT. A combination of the three lncRNAs and AFP showed the highest diagnostic accuracy for HCC, with an AUC of 0.998, sensitivity of 98.4%, and specificity of 100.0%. This combination showed a better diagnostic accuracy than the individual lncRNAs or AFP alone. Serum levels of the HOTAIR and ICR lncRNAs decreased significantly following surgery. CONCLUSIONS: Serum levels of the HOTAIR, BRM and ICR lncRNAs are potential prognostic markers for HCC. Upregulation of HOTAIR, BRM and ICR may facilitate early diagnosis and indicate poor prognosis for HCC. These lncRNAs could potentially serve as therapeutic targets for HCC. Combination of the three lncRNAs with AFP may increase the diagnostic accuracy for HCC. Further studies in larger cohorts of patients are needed to validate these findings.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante/genética , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Estudios Prospectivos , Curva ROC , alfa-Fetoproteínas/genéticaRESUMEN
We introduce end-to-end inverse design for multi-channel imaging, in which a nanophotonic frontend is optimized in conjunction with an image-processing backend to extract depth, spectral and polarization channels from a single monochrome image. Unlike diffractive optics, we show that subwavelength-scale "metasurface" designs can easily distinguish similar wavelength and polarization inputs. The proposed technique integrates a single-layer metasurface frontend with an efficient Tikhonov reconstruction backend, without any additional optics except a grayscale sensor. Our method yields multi-channel imaging by spontaneous demultiplexing: the metaoptics front-end separates different channels into distinct spatial domains whose locations on the sensor are optimally discovered by the inverse-design algorithm. We present large-area metasurface designs, compatible with standard lithography, for multi-spectral imaging, depth-spectral imaging, and "all-in-one" spectro-polarimetric-depth imaging with robust reconstruction performance (â² 10% error with 1% detector noise). In contrast to neural networks, our framework is physically interpretable and does not require large training sets. It can be used to reconstruct arbitrary three-dimensional scenes with full multi-wavelength spectra and polarization textures.
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BACKGROUND: Liver fibrosis is the early pathological manifestation of various chronic liver diseases (including schistosomiasis, alcoholic, viral, nonalcoholic, fatty liver, etc.), which can progress to cirrhosis and even liver cancer. Out of the 7.7 billion world population, approximately 2 billion individuals have evidence of hepatitis B virus (HBV) infection; of these, 350 to 400 million suffer from chronic HBV infection, accounting for about 5% of the global population. The global prevalence of hepatitis C is 3%. These figures indicate that liver fibrosis is quite common. METHODS: 98 patients with liver fibrosis were included in this study. The serum chitinase-3 Like Protein-1 (CHI3L1) level was measured by the double antibody Sandwich ELISA method. RESULTS: Serum levels of CHI3L1 were significantly different between no-fibrosis and fibrosis groups (P < 0.01). There was a strong correlation between the levels of CHI3L1, elastometry, hyaluronan, CIV (P < 0.01) and age and sex, TBIL, DBIL, ALB, AST, ALT, GGT, ALP, PLT, LN, PIINP, FIB-4, and APRI (P < 0.05). The expression of CHI3L1 was different from fibrosis grades S1, S3, and S4 (P < 0.05, P < 0.001). The expression of CHI3L1 was significantly different between F1 and F4 (P < 0.05). Serum CHI3L1 expression level can be a valuable metric for diagnosing liver fibrosis, with an AUC value of 0.812. Out of the 98 patients who had undergone liver puncture, 79 patients (30.38%) had ALT ≤ 2ULN. CONCLUSIONS: The expression level of serum CHI3L1 was significantly higher in patients with liver fibrosis than that in patients without liver fibrosis. The expression levels of serum CHI3L1 were different in different grades of liver fibrosis and increased with the severity of liver fibrosis. Serum CHI3L1 can distinguish early stage (S1) of liver fibrosis from late stage (S3-4) of liver fibrosis. Serum CHI3L1 combined with HA is even more effective in the diagnosis of S2-4 hepatic fibrosis. The diagnostic efficacy of serum CHI3L1 in patients with ALT ≤ 2ULN was better than that of the other non-invasive diagnostic models.
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Quitinasas , Hepatitis B Crónica , Humanos , Ácido Hialurónico , Cirrosis Hepática/patología , Hígado/patología , Biomarcadores , Virus de la Hepatitis B , Curva ROC , Proteína 1 Similar a Quitinasa-3RESUMEN
Background: Compound fuling granule (CFG) is a traditional Chinese medicine formula that is used for more than twenty years to treat ovarian cancer (OC) in China. However, the underlying processes have yet to be completely understood. This research is aimed at uncovering its molecular mechanism and identifying possible therapeutic targets. Methods: Significant genes were collected from Therapeutic Target Database and Database of Gene-Disease Associations. The components of CFG were analyzed by LC-MS/MS, and the active components of CFG were screened according to their oral bioavailability and drug-likeness index. The validated targets were extracted from PharmMapper and PubChem databases. Venn diagram and STRING website diagrams were used to identify intersection targets, and a protein-protein interaction network was prepared using STRING. The ingredient-target network was established using Cytoscape. Molecular docking was performed to visualize the molecule-protein interactions using PyMOL 2.3. Enrichment and pathway analyses were performed using FunRich software and Reactome pathway, respectively. Experimental validations, including CCK-8 assay, wound-scratch assay, flow cytometry, western blot assay, histopathological examination, and immunohistochemistry, were conducted to verify the effects of CFG on OC cells. Results: A total of 56 bioactive ingredients of CFG and 185 CFG-OC-related targets were screened by network pharmacology analysis. The potential therapeutic targets included moesin, glutathione S-transferase kappa 1, ribonuclease III (DICER1), mucin1 (MUC1), cyclin-dependent kinase 2 (CDK2), E1A binding protein p300, and transcription activator BRG1. Reactome analysis showed 51 signaling pathways (P < 0.05), and FunRich revealed 44 signaling pathways that might play an important role in CFG against OC. Molecular docking of CDK2 and five active compounds (baicalin, ignavine, lactiflorin, neokadsuranic acid B, and deoxyaconitine) showed that baicalin had the highest affinity to CDK2. Experimental approaches confirmed that CFG could apparently inhibit OC cell proliferation and migration in vitro; increase apoptosis; decrease the protein expression of MUC1, DICER1, and CDK2; and suppress the progression and distant metastasis of OC in vivo. DICER1, a tumor suppressor, is essential for microRNA synthesis. Our findings suggest that CFG may impair the production of miRNAs in OC cells. Conclusion: Based on network pharmacology, molecular docking, and experimental validation, the potential mechanism underlying the function of CFG in OC was explored, which supplies the theoretical groundwork for additional pharmacological investigation.
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Medicamentos Herbarios Chinos , Neoplasias Ováricas , Wolfiporia , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Cromatografía Liquida , ARN Helicasas DEAD-box , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Neoplasias Ováricas/tratamiento farmacológico , Ribonucleasa III , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: The data of the impact of tenofovir (TDF) on kidney damage in Chinese HIV-1 infected patients are limited. OBJECTIVE: The study aims to evaluate the incidence and risk factors of stage 3 chronic kidney disease (CKD) and rapid kidney function decline (RKFD) among Chinese HIV-1 infected patients starting with a TDF-based regimen. METHODS: We enrolled 797 TDF-initiated HIV-1-infected patients in a Chinese cohort. Kidney dysfunctions were defined as stage 3 CKD (eGFR < 60 mL/min/1.73 m2 during follow-up) and RKFD (eGFR decline > 10 mL/min/1.73 m2/year). A linear mixed-effects model was used to quantify the average eGFR change per 48 weeks. A generalized estimating equation regression analysis was conducted to determine the risk factors associated with renal dysfunction. The method of multiple imputations was used to reduce the bias caused by missing data. RESULTS: In this retrospective study, 14 (2%) patients experienced stage 3 CKD, and 272 (34%) individuals experienced RKFD during a median of 26 (IQR, 4-78; maximum 325) weeks follow-up period. The mean loss in eGFR per 48 weeks increased consistently over time, from -2.59 mL/min/1.73 m2 before 48 weeks to -17.61 mL/min/1.73 m2 after 288 weeks. For every 10 mL/min/1.73 m2 increase of eGFR, the risk of RKFD increased by 29% (95%CI: 18%, 40%). Each 10 years older and every 10 mL/min/1.73 m2 higher in baseline eGFR, the risk of stage 3 CKD increased to 1.56 (95% CI: 1.00, 2.43) and decreased by 65% (95% CI: 48%, 76%), respectively. Anemia and higher viral load were significantly associated with RKFD. The results were robust across a range of multiple imputation analyses. CONCLUSION: TDF-associated CKD is rare in HIV-1 infected Chinese adults. Longer TDF-exposed patients are more likely to have renal dysfunction, especially those with older age, anemia, lower baseline eGFR, and higher viral load.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Insuficiencia Renal Crónica , Adulto , Fármacos Anti-VIH/efectos adversos , Estudios de Cohortes , Tasa de Filtración Glomerular , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Incidencia , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Tenofovir/efectos adversosRESUMEN
Falling asleep at the wrong time can place an individual at risk of immediate physical harm. However, not sleeping degrades cognition and adaptive behavior. To understand how animals match sleep need with environmental demands, we used live-brain imaging to examine the physiological response properties of the dorsal fan-shaped body (dFB) following interventions that modify sleep (sleep deprivation, starvation, time-restricted feeding, memory consolidation) in Drosophila. We report that dFB neurons change their physiological response-properties to dopamine (DA) and allatostatin-A (AstA) in response to different types of waking. That is, dFB neurons are not simply passive components of a hard-wired circuit. Rather, the dFB neurons intrinsically regulate their response to the activity from upstream circuits. Finally, we show that the dFB appears to contain a memory trace of prior exposure to metabolic challenges induced by starvation or time-restricted feeding. Together, these data highlight that the sleep homeostat is plastic and suggests an underlying mechanism.
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Dopamina , Inanición , Animales , Drosophila , Neuronas , Plásticos , Sueño , Privación de SueñoRESUMEN
In recent years, studies have shown a close relationship between cardiomyocyte death and ferroptosis. Clioquinol (CQ) can inhibit ferroptosis. Porous lipid-poly (lactic-co-glycolic acid) (PLGA) microbubbles (MBs) were prepared by double emulsification (W1/O/W2) using 1,2-dioctadecanoyl-sn-glycero-3-phophocholine and PLGA as raw materials. Porous lipid-PLGA MBs were used as carriers to prepare CQ/PLGA MBs containing CQ. CQ/PLGA had the advantages of high drug loading, good biocompatibility, and sustained release. Our results showed that CQ/PLGA improved the effect of CQ and reduced its cytotoxicity. Under low-frequency ultrasound with certain parameters, CQ/PLGA showed steady-state cavitation, which increased the membrane permeability of mouse cardiomyocyte HL-1 to a certain extent and further prevented the process of ferroptosis in mouse cardiomyocyte HL-1.
