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Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1. Through genetic suppressor screens, we identified intragenic mutations in the OSM-3CA motor domain and mutations inhibiting the ciliary kinase DYF-5, both of which restored normal cilia in OSM-3CA-expressing animals. We showed that conformational changes in OSM-3CA prevent its entry into cilia, and OSM-3CA disposal requires its hyperactivity. Finally, we provide evidence that neurons also dispose of hyperactive kinesin-1 resulting from a clinic variant associated with amyotrophic lateral sclerosis, suggesting a widespread mechanism for regulating hyperactive kinesins.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Cilios , Cinesinas , Neuroglía , Animales , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Cinesinas/metabolismo , Cinesinas/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Neuroglía/metabolismo , Cilios/metabolismo , Neuronas/metabolismo , Mutación , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patologíaRESUMEN
The polyhydroxylated steroid phytohormone brassinosteroids (BRs) control many aspects of plant growth, development and responses to environmental changes. Plasma membrane (PM) H+-ATPase, the well-known PM proton pump, is a central regulator in plant physiology, which mediates not only plant growth and development, but also adaptation to stresses. Recent studies highlight that PM H+-ATPase is at least partly regulated via the BR signaling. Firstly, the BR cell surface receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and multiple key components of BR signaling directly or indirectly influence PM H+-ATPase activity. Secondly, the SMALL AUXIN UP RNA (SAUR) gene family physically interacts with BRI1 to enhance organ development of Arabidopsis by activating PM H+-ATPase. Thirdly, RNA-sequencing (RNA-seq) assays showed that the expression of some SAUR genes is upregulated under the light or sucrose conditions, which is related to the phosphorylation state of the penultimate residue of PM H+-ATPase in a time-course manner. In this review, we describe the structural and functional features of PM H+-ATPase, and summarize recent progress toward understanding the regulatory mechanism of PM H+-ATPase by BRs, and briefly introduce how PM H+-ATPase activity is modulated by its own biterminal regions and the post-translational modifications.
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BACKGROUND: Tibetan medicine Gaoyuan'an capsule (GYAC) is widely used to prevent pulmonary edema at high altitude, but the specific mechanism has not been explored. In this study, we analyzed the mechanism of GYAC in hypoxia tolerance, and provided a new idea for the prevention and treatment of altitude disease. METHODS: The effective components and corresponding targets of GYAC were screened out by the Chinese herbal medicine network database, and the key targets of hypoxia tolerance were retrieved by Genecards, OMIM and PubMed database. Cytoscape 3.7.2 was used to construct GYAC ingredient-target-hypoxia tolerance-related target network. GO function annotation and KEGG enrichment analysis were performed to predict the pathways in which target genes may be involved, and molecular docking was used to verify the binding ability of the compound to target genes. In vitro, the above results were further verified by molecular experiment. RESULTS: We found that GYAC can improve hypoxia tolerance by regulating various target genes, including IL6, IFNG, etc. The main regulatory pathways were HIF-1 signaling pathway. Molecular docking showed that the affinity between luteolin and target genes (IL6, IFNG) were better. In vitro, we observed that hypoxia can inhibit cell viability and promote apoptosis of H9C2 cell. And hypoxia can promote the expression of LDH. After the addition of luteolin, the decrease of cell viability, the increase of cell apoptosis, LDH release and the decrease of mitochondrial membrane potential were inhibited. Besides, inflammatory related factors (IL-6, IL-10, IL-2, IFNG and VEGFA) expression were also inhibited hypoxic cell models. CONCLUSIONS: The results of network pharmacology and molecular docking showed that luteolin, a monomeric component of GYAC, played a role in hypoxia tolerance through a variety of target genes, such as IL6, IFNG. What's more, we have discovered that luteolin can reduce the inflammatory response in cardiac myocytes, thereby alleviating mitochondrial damage, and ultimately enhancing the hypoxia tolerance of H9C2 cardiomyocytes.
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Medicamentos Herbarios Chinos , Interleucina-6 , Humanos , Simulación del Acoplamiento Molecular , Luteolina , Farmacología en Red , Hipoxia/tratamiento farmacológico , Hipoxia/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
INTRODUCTION: Ventricular septal defect (VSD) is the most common congenital heart malformation in children. This study aimed to investigate potential pathogenic genes associated with Tibetan familial VSD. METHODS: Whole genomic DNA was extracted from eight Tibetan children with VSD and their healthy parents (a total of 16 individuals). Whole-exome sequencing was performed using the Illumina HiSeq platform. After filtration, detection, and annotation, single nucleotide variations and insertion-deletion markers were examined. Comparative evaluations using the Sorting Intolerant from Tolerant, PolyPhen V2, Mutation Taster, and Combined Annotation Dependent Depletion databases were conducted to predict harmful mutant genes associated with the etiology of Tibetan familial VSD. RESULTS: A total of six missense mutations in genetic disease-causing genes associated with the development of Tibetan familial VSD were identified: activin A receptor type II-like 1 (c.652 C > T: p.R218 W), ATPase cation transporting 13A2 (c.1363 C > T: p.R455 W), endoplasmic reticulum aminopeptidase 1 (c.481 G > A: p.G161 R), MRI1 (c.629 G > A: p.R210Q), tumor necrosis factor receptor-associated protein 1 (c.224 G > A: p.R75H), and FBN2 (c.2260 G > A: p.G754S). The Human Gene Mutation Database confirmed activin A receptor type II-like 1, MRI1, and tumor necrosis factor receptor-associated protein 1 as pathogenic mutations, while FBN2 was classified as a probable pathogenic mutation. CONCLUSIONS: This novel study directly screens genetic variations associated with Tibetan familial VSD using whole-exome sequencing, providing new insights into the pathogenesis of VSD.
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Cardiopatías Congénitas , Defectos del Tabique Interventricular , Niño , Humanos , Secuenciación del Exoma , Tibet , Defectos del Tabique Interventricular/genética , Defectos del Tabique Interventricular/metabolismo , Receptores del Factor de Necrosis Tumoral/genéticaRESUMEN
Long non-coding metastasis-associated lung adenocarcinoma transcript (lnc-Malat1) emerges as a novel regulator in skeletal muscle development, while its function and the related mechanism is not fully revealed yet. In this study, knockdown of lnc-Malat1 by siRNA significantly inhibited the expression of myoblast marker genes (MyHC, MyoD, and MyoG) and slow muscle fiber marker genes (MyHC I), together with repressed expression of mitochondria-related genes COX5A, ACADM, CPTA1, FABP3, and NDUFA1. Overexpression of lnc-Malat1 exerted an opposite effect, promoting myoblast differentiation and slow muscle fiber formation. Dual luciferase reporter assay revealed a direct interaction between lnc-Malat1 and miR-129-5p, and overexpression of lnc-Malat1 significantly inhibited miR-129-5p expression, thereby elevating the expression of Mef2a, miR-129-5p target protein. In addition, enforced expression of lnc-Malat1 restored the inhibitory effect of miR-129-5p on myoblast differentiation and MyHC I expression. Taken together, our results suggest that lnc-Malat1 promotes myoblast differentiation, and maintains the slow muscle fiber phenotype via adsorbing miR-129-5p.
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MicroARNs , Fibras Musculares Esqueléticas , Bioensayo , Diferenciación Celular/genética , ADN Mitocondrial , MicroARNs/genéticaRESUMEN
In this cohort of 217 bladder cancer patients and 484 healthy controls, we explored the association between CYP24A1 variants (rs2762934, rs1570669, rs6068816, rs2296241) and bladder cancer risk in the Chinese Han population. Utilizing the Agena MassARRAY system, we genotyped four selected CYP24A1 polymorphisms. Logistic regression revealed a significant association of rs2762934 and rs1570669 with elevated bladder cancer risk, while rs6068816 exhibited a protective effect. Bioinformatics analysis of CYP24A1 expression in normal and cancerous bladder tissues indicated higher expression in normal tissue. In conclusion, our findings highlight the potential role of CYP24A1 variants in bladder cancer susceptibility.
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This paper predicts the network security posture of an ICS, focusing on the reliability of Industrial Control Systems (ICSs). Evidence reasoning (ER) and belief rule base (BRB) techniques are employed to establish an ICS network security posture prediction model, ensuring the secure operation and prediction of the ICS. This model first integrates various information from the ICS to determine its network security posture value. Subsequently, through ER iteration, information fusion occurs and serves as an input for the BRB prediction model, which necessitates initial parameter setting by relevant experts. External factors may influence the experts' predictions; therefore, this paper proposes the Projection Equalization Optimization (P-EO) algorithm. This optimization algorithm updates the initial parameters to enhance the prediction of the ICS network security posture through the model. Finally, industrial datasets are used as experimental data to improve the credibility of the prediction experiments and validate the model's predictive performance in the ICS. Compared with other methods, this paper's prediction model demonstrates a superior prediction accuracy. By further comparing with other algorithms, this paper has a certain advantage when using less historical data to make predictions.
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Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The whole concept of NAFLD has now moved into metabolic dysfunction-associated fatty liver disease (MAFLD) to emphasize the strong metabolic derangement as the basis of the disease. Several studies have suggested that hepatic gene expression was altered in NAFLD and NAFLD-related metabolic comorbidities, particularly mRNA and protein expression of phase I and II drug metabolism enzymes (DMEs). NAFLD may affect the pharmacokinetic parameters. However, there were a limited number of pharmacokinetic studies on NAFLD at present. Determining the pharmacokinetic variation in patients with NAFLD remains challenging. Common modalities for modeling NAFLD included: dietary induction, chemical induction, or genetic models. The altered expression of DMEs has been found in rodent and human samples with NAFLD and NAFLD-related metabolic comorbidities. We summarized the pharmacokinetic changes of clozapine (CYP1A2 substrate), caffeine (CYP1A2 substrate), omeprazole (Cyp2c29/CYP2C19 substrate), chlorzoxazone (CYP2E1 substrate), midazolam (Cyp3a11/CYP3A4 substrate) in NAFLD. These results led us to wonder whether current drug dosage recommendations may need to be reevaluated. More objective and rigorous studies are required to confirm these pharmacokinetic changes. We have also summarized the substrates of the DMEs aforementioned. In conclusion, DMEs play an important role in the metabolism of drugs. We hope that future investigations should focus on the effect and alteration of DMEs and pharmacokinetic parameters in this special patient population with NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Animales , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP1A2/farmacología , Hígado/metabolismo , Modelos AnimalesRESUMEN
Lithium-sulfur batteries (LSBs) are widely regarded as reliable novel secondary batteries due to their low price and high capacity. Nevertheless, the notorious "shuttle effect" limits the commercialization of LSBs. In order to solve this problem, we fabricated a Ni3S2-Ni/C composite through carbonization, vulcanization and hydrothermal reactions by using a Ni-MOF precursor and applied it as a separator modification layer to enhance the electrochemical properties of LSBs. To further increase the conductivity of the material, a small amount of GO was added during the experiment. The prepared material was also used as separator modified coating material to optimize the electrochemical performance of LSBs. The as prepared Ni3S2-Ni/C(GO) composite shows good conductivity and has a superior porous structure and abundant active sites. Lithium polysulfides (LPs) can be physically confined and chemically adsorbed, what is more, the Ni and Ni3S2 active sites enable fast conversion of LPs which further optimizes the rate performance. From the cycle performance measurement, the initial discharge specific capacity of the Ni3S2-Ni/C(GO) modified separator battery is found to be 1263.4, 1181.5, 1090.6, and 840.3 mA h g-1 at 0.05, 0.1, 0.3 and 0.5C, respectively. After 400 charge/discharge cycles at 0.5C, the capacity remains at 483.6mA h g-1 with a capacity retention ratio of 57.56%.
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Intramuscular fat content is an important factor that determines meat quality in pigs. In recent years, epigenetic regulation has increasingly studied the physiological model of intramuscular fat. Although long noncoding RNAs (lncRNAs) play essential roles in various biological processes, their role in intramuscular fat deposition in pigs remains largely unknown. In this study, intramuscular preadipocytes in the longissimus dorsi and semitendinosus of Large White pigs were isolated and induced into adipogenic differentiation in vitro. High-throughput RNA-seq was carried out to estimate the expression of lncRNAs at 0, 2 and 8 days post-differentiation. At this stage, 2135 lncRNAs were identified. KEGG analysis showed that the differentially expressed lncRNAs were common in pathways involved with adipogenesis and lipid metabolism. lnc_000368 was found to gradually increase during the adipogenic process. Reverse-transcription quantitative polymerase chain reaction and a western blot revealed that the knockdown of lnc_000368 significantly repressed the expression of adipogenic genes and lipolytic genes. As a result, lipid accumulation in porcine intramuscular adipocytes was impaired by the silencing of lnc_000368. Overall, our study identified a genome-wide lncRNA profile related to porcine intramuscular fat deposition, and the results suggest that lnc_000368 is a potential target gene that might be targeted in pig breeding in the future.
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Músculos Isquiosurales , ARN Largo no Codificante , Porcinos/genética , Animales , Adipogénesis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Músculos Isquiosurales/metabolismo , Epigénesis Genética , Adipocitos/metabolismoRESUMEN
The traditional Transformer model primarily employs a self-attention mechanism to capture global feature relationships, potentially overlooking local relationships within sequences and thus affecting the modeling capability of local features. For Support Vector Machine (SVM), it often requires the joint use of feature selection algorithms or model optimization methods to achieve maximum classification accuracy. Addressing the issues in both models, this paper introduces a novel network framework, CTSF, specifically designed for Industrial Internet intrusion detection. CTSF effectively addresses the limitations of traditional Transformers in extracting local features while compensating for the weaknesses of SVM. The framework comprises a pre-training component and a decision-making component. The pre-training section consists of both CNN and an enhanced Transformer, designed to capture both local and global features from input data while reducing data feature dimensions. The improved Transformer simultaneously decreases certain training parameters within CTSF, making it more suitable for the Industrial Internet environment. The classification section is composed of SVM, which receives initial classification data from the pre-training phase and determines the optimal decision boundary. The proposed framework is evaluated on an imbalanced subset of the X-IIOTID dataset, which represent Industrial Internet data. Experimental results demonstrate that with SVM using both "linear" and "rbf" kernel functions, CTSF achieves an overall accuracy of 0.98875 and effectively discriminates minor classes, showcasing the superiority of this framework.
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Photoperiod strictly controls vegetative and reproductive growth stages in soybean (Glycine max). A soybean GmRAV (Related to ABI3/VP1) transcription factor containing both AP2 and B3 domains was shown to be a key component of this process. We identified six polymorphisms in the GmRAV promoter that showed significant association with flowering time and maturity of soybean in one or multiple environments. Soybean varieties with minor polymorphism exhibited a longer growth period contributing to soybean adaptation to lower latitudes. The cis-acting element GT1CONSENSUS motif of the GmRAV promoter controlled the growth period, and the major allele in this motif shortened duration of late reproductive stages by reducing GmRAV expression levels. Three GmRAV-overexpressing (GmRAV-ox) transgenic lines displayed later ï¬owering time and maturity, shorter height and fewer numbers of leaves compared with control plants, whereas transgenic inhibition of GmRAV expression resulted in earlier ï¬owering time and maturity and increased plant height. Combining DNA affinity purification sequencing and RNA sequencing analyses revealed 154 putative target genes directly bound and transcriptionally regulated by GmRAV. Two GmRAV binding motifs [C(A/G)AACAA(G/T)A(C/T)A(G/T)] and [C(T/A)A(C)C(T/G)CTG] were identiï¬ed, and acting downstream of E3E4, GmRAV repressed GmFT5a transcriptional activity through binding a CAACA motif, thereby delaying soybean growth and extending both vegetative and reproductive phases.
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Adaptación Biológica , Flores/crecimiento & desarrollo , Glycine max/genética , Fotoperiodo , Proteínas de Plantas/genética , Factores de Transcripción/genética , Flores/genética , Proteínas de Plantas/metabolismo , Glycine max/crecimiento & desarrollo , Glycine max/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Maize (Zea mays L.) is the most important food crop in the world, with significant acreage and production across the globe. However, it is affected by low temperatures throughout its growth process, especially during germination. Therefore, it is important to identify more QTLs or genes associated with germination under low-temperature conditions. For the QTL analysis of traits related to low-temperature germination, we used a high-res genetic map of 213 lines of the intermated B73 × Mo17 (IBM) Syn10 doubled haploid (DH) population, which had 6618 bin markers. We detected 28 QTLs of eight phenotypic characteristics associated with low-temperature germination, while they explained the phenotypic contribution rate of 5.4 ~ 13.34%. Additionally, 14 overlapping QTLs produced six QTL clusters on every chromosome, except for 8 and 10. RNA-Seq found six genes related to low-temperature tolerance in these QTLs, while qRT-PCR analysis demonstrated that the expression trends of the Zm00001d045568 gene in the LT_BvsLT_M group and the CK_BvsCK_M group were highly significantly different at all four-time points (P < 0.01), and encoded the RING zinc finger protein. It was located on qRTL9-2 and qRSVI9-1 and is related to the total length and simple vitality index. These results provided potential candidate genes for further gene cloning and improving the low-temperature tolerance of maize. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01297-6.
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Aim: This study was designed to evaluate the contribution of GBAP1 variants to gastric cancer (GC) risk in a Chinese Han population. Methods: The genotypes of GBAP1 polymorphisms were detected using the Agena MassARRAY platform. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs. Results: GBAP1 rs140081212 (OR = 0.51, p = 4.50 × 10-07), rs1057941 (OR = 0.48, p = 1.19 × 10-08) and rs2990220 (OR = 0.46, p = 7.34 × 10-09) contribute to reduced GC risk, especially gastric adenocarcinoma. Interestingly, the contribution of GBAP1 variants to GC susceptibility was associated with age, sex, BMI, smoking and drinking. Conclusion: This research suggested that GBAP1 polymorphisms might provide a protective effect against GC occurrence in a Chinese Han population.
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Neoplasias Gástricas , Estudios de Casos y Controles , China/epidemiología , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
An integrated custom cross-response sensing array has been developed combining the algorithm module's visible machine learning approach for rapid and accurate pathogenic microbial taxonomic identification. The diversified cross-response sensing array consists of two-dimensional nanomaterial (2D-n) with fluorescently labeled single-stranded DNA (ssDNA) as sensing elements to extract a set of differential response profiles for each pathogenic microorganism. By altering the 2D-n and different ssDNA with different sequences, we can form multiple sensing elements. While interacting with microorganisms, the competition between ssDNA and 2D-n leads to the release of ssDNA from 2D-n. The signals are generated from binding force driven by the exfoliation of either ssDNA or 2D-n from the microorganisms. Thus, the signal is distinguished from different ssDNA and 2D-n combinations, differentiating the extracted information and visualizing the recognition process. Fluorescent signals collected from each sensing element at the wavelength around 520 nm are applied to generate a fingerprint. As a proof of concept, we demonstrate that a six-sensing array enables rapid and accurate pathogenic microbial taxonomic identification, including the drug-resistant microorganisms, under a data size of n = 288. We precisely identify microbial with an overall accuracy of 97.9%, which overcomes the big data dependence for identifying recurrent patterns in conventional methods. For each microorganism, the detection concentration is 105 ~ 108 CFU/mL for Escherichia coli, 102 ~ 107 CFU/mL for E. coli-ß, 103 ~ 108 CFU/mL for Staphylococcus aureus, 103 ~ 107 CFU/mL for MRSA, 102 ~ 108 CFU/mL for Pseudomonas aeruginosa, 103 ~ 108 CFU/mL for Enterococcus faecalis, 102 ~ 108 CFU/mL for Klebsiella pneumoniae, and 103 ~ 108 CFU/mL for Candida albicans. Combining the visible machine learning approach, this sensing array provides strategies for precision pathogenic microbial taxonomic identification. ⢠A molecular response differential profiling (MRDP) was established based on custom cross-response sensor array for rapid and accurate recognition and phenotyping common pathogenic microorganism. ⢠Differential response profiling of pathogenic microorganism is derived from the competitive response capacity of 6 sensing elements of the sensor array. Each of these sensing elements' performance has competitive reaction with the microorganism. ⢠MRDP was applied to LDA algorithm and resulted in the classification of 8 microorganisms.
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Escherichia coli , Nanoestructuras , ADN de Cadena Simple , Aprendizaje Automático , Nanoestructuras/químicaRESUMEN
Non-collinear stimulated Brillouin scattering (SBS) amplification can obtain high peak power Stokes output while ensuring the stability, but the frequency mismatch reduces the energy conversion efficiency of the system. In this paper, a dual-frequency pulse laser based on acousto-optic crystal modulation is designed. The output pulse pair can be used as pump and Stokes light, respectively, which realizes the active frequency matching of the gain medium Brillouin frequency shift during the SBS amplification process and helps to maintain ideal energy conversion efficiency. The dual-frequency laser finally produced a laser pulse pair with a pulse width adjustment range of 100 ps-50 ns, a frequency shift range of 0 GHz-2 GHz, and the polarization extinction ratio (PER) reaches 20.82dB.
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Personalized medicine, the treatment best suited for an individual, is a hot field of clinical research in the world. Many recent studies have shown that genetic variations have a great influence on the treatment. This study aimed to identify the distribution differences of very important pharmacogene (VIP) variants between the Tibetan population and the other 26 populations from the 1000 Genomes project. Based on the PharmGKB database, we successfully genotyped 50 VIP variants located in 27 genes in the Tibetan population. We also compared the genotype frequencies of VIP variants between Tibetan population and the other 26 populations. Without adjustment, the Chi-square test showed that the only significant variant between Tibetans and every other group was rs1801159 in dihydropyrimidine dehydrogenase (DPYD), followed by rs1800566 in NAD(P)H quinone dehydrogenase 1 (NQO1) and rs1051296 in solute carrier family 19 member 1 (SLC19A1). After Bonferroni's multiple adjustments, the genotype frequencies distribution of DPYD rs1801159 was found to be different in Tibetans compared to the other 26 groups, apart from ACB and ASW. Moreover, genetic structure/F-statistics (Fst) analysis and the phylogenetic tree illustrated that Tibetans had a closer affinity with CDX, CHB, CHS, JPT and KHV. Our data will complement pharmacogenomics information of the Tibetan population and provide theoretical support for the realization of individualized medical treatment for Tibetans in the future.
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Frecuencia de los Genes , Filogenia , Pueblo Asiatico , Genotipo , Humanos , TibetRESUMEN
A novel trench-assisted dual-mode multi-core fiber with large-mode-field-area is proposed. The structure consists of 17 conventional cores and two air holes according to a regular hexagon, which can realize strict dual-mode transmission. The structural parameters' effect on mode transmission characteristics, mode-field-area, and bending loss are analyzed systematically. By optimizing the structural parameters, the mode-field-area of the fundamental mode can reach ${2100.619}\;{{\unicode{x00B5}{\rm m}}^2}$. The introduction of the trench with a lower refractive index than cladding can reduce the bending loss to ${9.88} \times {{10}^{- 4}}\;{\rm dB}/{\rm m}$ when the bending radius is 2.3 cm. Besides, the structural design is flexible, and the manufacturing process is simple, which has broad application prospects.
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The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m2) and cisplatin (30-35 mg/m2 or 40-50 mg/m2) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Vinorelbina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Inyecciones , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Vinorelbina/administración & dosificación , Vinorelbina/efectos adversosRESUMEN
Variations of gene expression levels play an important role in tumors. There are numerous methods to identify differentially expressed genes in high-throughput sequencing. Several algorithms endeavor to identify distinctive genetic patterns susceptable to particular diseases. Although these processes have been proved successful, the probability that the number of non-differentially expressed genes measured by false discovery rate (FDR) has a large standard deviation, and the misidentification rate (type I error) grows rapidly when the number of genes to be detected become larger. In this study we developed a new method, Unit Gamma Measurement (UGM), accounting for multiple hypotheses test statistics distribution, which could reduce the dependency problem. Simulated expression profile data and breast cancer RNA-Seq data were utilized to testify the accuracy of UGM. The results show that the number of non-differentially expressed genes identified by the UGM is very close to the real-evidence data, and the UGM also has a smaller standard error, range, quartile range and RMS error. In addition, the UGM can be used to screen many breast cancer-associated genes, such as BRCA1, BRCA2, PTEN, BRIP1, etc., provides better accuracy, robustness and efficiency, the method of identification differentially expressed genes in high-throughput sequencing.