RESUMO
In recent years, the research of autonomous driving and mobile robot technology is a hot research direction. The ability of simultaneous positioning and mapping is an important prerequisite for unmanned systems. Lidar is widely used as the main sensor in SLAM (Simultaneous Localization and Mapping) technology because of its high precision and all-weather operation. The combination of Lidar and IMU (Inertial Measurement Unit) is an effective method to improve overall accuracy. In this paper, multi-line Lidar is used as the main data acquisition sensor, and the data provided by IMU is integrated to study robot positioning and environment modeling. On the one hand, this paper proposes an optimization method of tight coupling of lidar and IMU using factor mapping to optimize the mapping effect. Use the sliding window to limit the number of frames optimized in the factor graph. The edge method is used to ensure that the optimization accuracy is not reduced. The results show that the point plane matching mapping method based on factor graph optimization has a better mapping effect and smaller error. After using sliding window optimization, the speed is improved, which is an important basis for the realization of unmanned systems. On the other hand, on the basis of improving the method of optimizing the mapping using factor mapping, the scanning context loopback detection method is integrated to improve the mapping accuracy. Experiments show that the mapping accuracy is improved and the matching speed between two frames is reduced under loopback mapping. However, it does not affect real-time positioning and mapping, and can meet the requirements of real-time positioning and mapping in practical applications.
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Rheumatoid arthritis (RA) is a common autoimmune disease that can lead to severe joint damage and disability. And early diagnosis and treatment of RA can avert or substantially slow the progression of joint damage in up to 90% of patients, thereby preventing irreversible disability. Previous research indicated that 50% of the risk for the development of RA is attributable to genetic factors, but the pathogenesis is not well understood. Thus, it is urgent to identify biomarkers to arrest RA before joints are irreversibly damaged. Here, we first use the Robust Rank Aggregation method (RRA) to identify the differentially expressed genes (DEGs) between RA and normal samples by integrating four public RA patients' mRNA expression data. Subsequently, these DEGs were used as the input for the weighted gene co-expression network analysis (WGCNA) approach to identify RA-related modules. The function enrichment analysis suggested that the RA-related modules were significantly enriched in immune-related actions. Then the hub genes were defined as the candidate genes. Our analysis showed that the expression levels of candidate genes were significantly associated with the RA immune microenvironment. And the results indicated that the expression of the candidate genes can use as predictors for RA. We hope that our method can provide a more convenient approach for the early diagnosis of RA.
Assuntos
Artrite Reumatoide , Genes Essenciais , Humanos , Artrite Reumatoide/genética , Biomarcadores , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de GenesRESUMO
RATIONALE: Advanced signet ring cell (SRC) carcinoma has a worse prognosis. Therefore, early diagnosis and prevention is particularly important; SRC tumors have lower R0 resection rate and are thought to be less chemosensitive than non-SRCC. Consequently, a novel postoperative adjuvant treatment is urgently needed to improve clinical outcomes. PATIENT CONCERNS: A 41-year-old female with advanced gastric SRC carcinoma was treated with radical gastrectomy and oxaliplatin-based regimen for 6 cycles after surgery. She was suspected of recurrence with the high level of carbohydrate antigen (CA) 72-4. DIAGNOSES: The gastroscopy revealed SRC carcinoma of gastric antrum and poorly differentiated adenocarcinoma in some areas. The diagnosis of postoperative pathology report was gastric cancer with stage III C (T4a, N3a, M0). INTERVENTIONS: The level of CA72-4 rapidly increased during the 2 follow-up after the completion of conventional treatment, ex vivo-cultured allogeneic natural killer (NK) cell infusion was offered to prevent recurrence. OUTCOMES: Intravenous injections of NK cells combination with surgical treatment and chemotherapy showed therapeutic effects in this patient with possible relapse. The patient remained disease-free 46âmonths after the infusion of NK cells until the latest follow-up. LESSONS: CA72-4 appeared to be the most sensitive and specific marker in the gastric cancer patient, and the high level of CA72-4 may indicate the risk of recurrence. This case report provide rationale for NK cell infusion following the rapid increase of CA72-4 to prevent recurrence.
Assuntos
Carcinoma de Células em Anel de Sinete/terapia , Gastrectomia , Células Matadoras Naturais/transplante , Cuidados Pós-Operatórios/métodos , Neoplasias Gástricas/terapia , Adulto , Antígenos Glicosídicos Associados a Tumores/sangue , Antígenos Glicosídicos Associados a Tumores/imunologia , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/imunologia , Carcinoma de Células em Anel de Sinete/patologia , Terapia Combinada/métodos , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Transplante Homólogo , Resultado do TratamentoRESUMO
PURPOSE: The human peroxiredoxin-5 (hPRDX5) is a member of the family of antioxidant enzymes, which could resist immunosuppression by promoting immune organs development, lymphocyte proliferation and up-regulation of the levels of serum cytokines. However, being a recombinant protein, the hPRDX5 exhibits some problems including the high production cost and bad tissue penetration. Compared to macromolecular therapeutic agents, synthetic peptides have several advantages as drug candidates, such as lower manufacturing costs, reduced immunogenicity, and better organ or tumor penetration. The purpose of this research was to design the novel peptides come from hPRDX5 that can block the interaction of PD-1 and PD-L1. METHODS: Herein in this work, we firstly confirmed the inhibitory activity of hPRDX5 on the binding of PD-L1 to PD-1 based on the previous observation, subsequently, in silico proteolysis and rational design (such as alanine scanning mutagenesis and truncation) were used to automate the design of new peptides derived from hPRDX5 with anti-tumour activity. RESULTS: We found that the most potent peptide could block the PD-1/PD-L1 interaction effectively with an IC50 of 0.646 µM, and could restore the function of Jurkat T cells which had been suppressed by stimulated HCT116 cells. Moreover, experiments with tumor-bearing mice models showed that the peptide IMB-P6-10 could effectively inhibit tumor growth and showed extraordinary low acute toxicity in vivo. CONCLUSIONS: The peptides described in this paper may provide novel low-molecular-weight drug candidates for cancer immunotherapy.
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Antígeno B7-H1/antagonistas & inibidores , Neoplasias do Colo/tratamento farmacológico , Desenho de Fármacos , Descoberta de Drogas , Fragmentos de Peptídeos/farmacologia , Peroxirredoxinas/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , Animais , Apoptose , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Simulação por Computador , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fragmentos de Peptídeos/química , Proteólise , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Aberrant activation of Bruton's tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds. Compound BGB-3111 (31a, Zanubrutinib) demonstrates (i) potent activity against BTK and excellent selectivity over other TEC, EGFR and Src family kinases, (ii) desirable ADME, excellent in vivo pharmacodynamic in mice and efficacy in OCI-LY10 xenograft models.
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Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Antineoplásicos/farmacologia , Descoberta de Drogas , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Tirosina Quinase da Agamaglobulinemia/metabolismo , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Piperidinas/síntese química , Piperidinas/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Ratos , Relação Estrutura-AtividadeRESUMO
Azacoccones A-E (1-5), five new aza-epicoccone derivatives, were isolated from the culture of Aspergillus flavipes. Their structures were determined by extensive NMR spectroscopic analyses and the absolute configuration of 5 was determined by electronic circular dichroism (ECD) calculation. Compounds 1-5 are proposed to be generated via a Pictet-Spengler reaction-based biosynthetic route starting from the precursor flavipin. Pictet-Spengler reaction is rarely found in the fungal kingdom, which indicated the distinctive nature of 1-5. Compounds 3 and 5 exhibit significant free radical scavenging activities with IC50 values of 4.0 and 2.4µg/mL, respectively, which are better than the positive control trolox (4.55µg/mL).
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Aspergillus/química , Polifenóis/isolamento & purificação , Dicroísmo Circular , Sequestradores de Radicais Livres/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
A total of 72 isolates of root-associated/endophytic (RAE) bacteria were isolated from peanut plants grown in the main producing areas of 6 provinces in China. The 16S rRNA gene sequences of these isolates were determined and phylogenetic analyses revealed that 72 isolates belonged to the classes Bacilli (49 isolates) and Gammaproteobacteria (23 isolates). The majority of RAE bacteria in Bacilli belonged to 2 genera, Bacillus and Lysinibacillus (48 and 1) while those in Gammaproteobacteria belonged to the genera Enterobacter, Serratia, Stenotrophomonas, and Pseudomonas (7, 11, 3 and 2 isolates, respectively). This is the first report of Lysinibacillus xylanilyticus isolate as biocontrol agent against AFs. All of the selected RAE bacteria showed inhibitory activities against Aspergillus parasiticus (A. parasiticus) growth and/or aflatoxins (AFs) production by visual agar plate assay and tip culture method. Most of the RAE bacteria strains (96 % strains) were determined to have decreased mycelia growth or AFs production levels by >50 % (p < 0.05). Bacterial isolates were further characterized for chitinolytic activity and 22 strains (30 % strains) of identified RAE bacteria degraded colloidal chitin on the chitin medium plate. Ten selected chitinolytic RAE bacteria were tested for antifungal activity on peanuts and most of them significantly decreased mycelial growth and AFs production levels by >90 %. These results showed a wide distribution of biological control bacteria against AFs in Chinese peanut main producing areas and the selected RAE bacteria could potentially be utilized for the biocontrol of toxicogenic fungi.
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Aflatoxinas/antagonistas & inibidores , Arachis/microbiologia , Bacillus/fisiologia , Quitina/metabolismo , Gammaproteobacteria/fisiologia , Aspergillus/crescimento & desenvolvimento , Bacillus/genética , Bacillus/isolamento & purificação , Biodiversidade , China , Quitina/genética , Endófitos/genética , Endófitos/isolamento & purificação , Endófitos/fisiologia , Gammaproteobacteria/isolamento & purificação , Micélio/crescimento & desenvolvimento , Filogenia , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
Objective. To investigate the effect of simulated weightlessness on serum alkaline phosphatase (ALP), calcium, magnesium, chlorine and phosphorus. Method. 6 healthy males, aged 24.8 +/- 6.1, were exposed to -6 degrees HDT bed rest for 21 d. Activity of serum alkaline phosphatase, serum contents of calcium (Ca), magnesium (Mg), chlorine (Cl) and phosphorus (P) ions were assayed before HDT (d-3), on the 3rd, 10th and 21st day during HDT and after HDT (d+2). Ca was measured by methyl thymol blue method, P was determined with ultraviolet spectrophotography, determination of Mg and Cl were made with enzyme method, ALP was examined with 4-nitrobenzene phosphate method. Result. Serum Ca2+ levels were significantly higher at d10, d2l and d+2 than the value of d-3 (P<0.01). P3+ levels declined significantly on d2l as compared with d-3 (P<0.01). During the HDT and after HDT, Mg2+ declined to a level below that before HDT (P<0.05 or P<0.01). Cl- were significantly higher at d2l and d+2 than the value of d-3 (P<0.01). ALP level was higher on d2l than on d-3 (P<0.01). Conclusion. 21 d HDT induced increase of Ca, Cl, ALP, and decline of Mg and P. The changes may reflect the imbalance of metabolism.