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1.
Comput Intell Neurosci ; 2022: 8568917, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535183

RESUMO

Industrial IoT (IIoT) in Industry 4.0 integrates everything at the level of information technology with the level of technology of operation and aims to improve Business to Business (B2B) services (from production to public services). It includes Machine to Machine (M2M) interaction either for process control (e.g., factory processes, fleet tracking) or as part of self-organizing cyber-physical distributed control systems without human intervention. A critical factor in completing the abovementioned actions is the development of intelligent software systems in the context of automatic control of the business environment, with the ability to analyze in real-time the existing equipment through the available interfaces (hardware-in-the-loop). In this spirit, this paper presents an advanced intelligent approach to real-time monitoring of the operation of industrial equipment. A hybrid novel methodology that combines memory neural networks is used, and Bayesian methods that examine a variety of characteristic quantities of vibration signals that are exported in the field of time, with the aim of real-time detection of abnormalities in active IIoT equipment are also used.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Teorema de Bayes , Redes de Comunicação de Computadores , Humanos , Indústrias
2.
Eur J Dent Educ ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579548

RESUMO

BACKGROUND: Static computer-assisted surgery (s-CAIS) and dynamic computer-assisted implant surgery (d-CAIS) are the main digital approaches in guiding dental implant placement. PURPOSE: The aim of this study was to explore and compare the learning curves for s-CAIS and d-CAIS by beginners. MATERIALS AND METHODS: Three dental students used each dental model for drilling five positions with missing teeth. Operators performed the drilling test for five sets of dental models with an interval of 7 ± 1 days assisted by the d-CAIS system. After a six-month break, the same students performed the drilling test again in the same way but with the s-CAIS system. A total of thirty models were used, and 150 implants were inserted. The operation time and relative deviations were recorded and calculated. Correlations between various deviation parameters and attempts were tested with independent-samples Kruskal-Wallis tests. RESULTS: A significant difference between the two groups was found in the operation time (P < 0.001). For accuracy, the difference was found in the first attempt of coronal and apical deviations but disappeared as the training went on. As the practice progressed, improvement was evident in the d-CAIS group but not in the s-CAIS group. When reaching the plateau stage of the learning curve of the d-CAIS group (after five attempts), the influence of different methods of guidance was limited between the two groups. CONCLUSIONS: A learning curve effect was found in d-CAIS but not in s-CAIS in vitro tests by beginners. The operating procedure of dynamic navigated and static template-guided implant placement was easy to master.

3.
Front Oncol ; 12: 870914, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444934

RESUMO

Objectives: Triple-negative breast cancer (TNBC) is defined as a highly aggressive type of breast cancer which lacks specific biomarkers and drug targets. Damage-associated molecular pattern (DAMP)-induced immunogenic cell death (ICD) may influence the outcome of immunotherapy for TNBC patients. This study aims to develop a DAMPs gene signature to classify TNBC patients and to further predict their prognosis and immunotherapy outcome. Methods: We identified the DAMPs-associated subtypes of 330 TNBCs using K-means analysis. Differences in immune status, genomic alterations, and predicted immunotherapy outcome were compared among each subtype. Results: A total of 330 TNBCs were divided into three subtypes according to DAMPs gene expression: the nuclear DAMPs subtype, featuring the upregulation of nuclear DAMPs; the inflammatory DAMPs subtype, characterized by the gene set enrichment of the adaptive immune system and cytokine signaling in the immune system; and the DAMPs-suppressed subtype, having the lowest level of ICD-associated DAMPs. Among them, the inflammatory subtype patients had the most favorable survival, while the DAMPs-suppressed subtype was associated with the worst prognosis. The DAMPs subtyping system was successfully validated in the TCGA cohort. Furthermore, we systemically revealed the genomic alterations among the three DAMPs subtypes. The inflammatory DAMPs subtype was predicted to have the highest response rate to immunotherapy, suggesting that the constructed DAMPs clustering had potential for immunotherapy efficacy prediction. Conclusion: We established a novel ICD-associated DAMPs subtyping system in TNBC, and DAMPs expression might be a valuable biomarker for immunotherapy strategies. Our work could be helpful to the development of new immunomodulators and may contribute to the development of precision immunotherapy for TNBC.

4.
Biomed Pharmacother ; 150: 112983, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35453009

RESUMO

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among epilepsy patients, occurring even more frequently in cases with anti-epileptic drug resistance. Despite some advancements in characterizing SUDEP, the underlying mechanism remains incompletely understood. This review summarizes the latest advances in our understanding of the pathogenic mechanisms of SUDEP, in order to identify possible targets for the development of new strategies to prevent SUDEP. Based on our previous research along with the current literature, we focus on the role of sleep-disordered breathing (SDB) and its related neural mechanisms to consider the possible roles of monoaminergic neurons in the modulation of respiration during sleep and the occurrence of SUDEP. Overall, this review suggests that targeting the monoaminergic neurons is a promising approach to preventing SUDEP. The proposed roles of SDB and related monoaminergic neural mechanisms in SUDEP provide new insights for explaining the pathogenesis of SUDEP.

5.
Nucleic Acids Res ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35466371

RESUMO

Site-specific incorporation of distinct non-canonical amino acids into proteins via genetic code expansion requires mutually orthogonal aminoacyl-tRNA synthetase/tRNA pairs. Pyrrolysyl-tRNA synthetase (PylRS)/tRNAPyl pairs are ideal for genetic code expansion and have been extensively engineered for developing mutually orthogonal pairs. Here, we identify two novel wild-type PylRS/tRNAPyl pairs simultaneously present in the deep-rooted extremely halophilic euryarchaeal methanogen Candidatus Methanohalarchaeum thermophilum HMET1, and show that both pairs are functional in the model halophilic archaeon Haloferax volcanii. These pairs consist of two different PylRS enzymes and two distinct tRNAs with dissimilar discriminator bases. Surprisingly, these two PylRS/tRNAPyl pairs display mutual orthogonality enabled by two unique features, the A73 discriminator base of tRNAPyl2 and a shorter motif 2 loop in PylRS2. In vivo translation experiments show that tRNAPyl2 charging by PylRS2 is defined by the enzyme's shortened motif 2 loop. Finally, we demonstrate that the two HMET1 PylRS/tRNAPyl pairs can simultaneously decode UAG and UAA codons for incorporation of two distinct noncanonical amino acids into protein. This example of a single base change in a tRNA leading to additional coding capacity suggests that the growth of the genetic code is not yet limited by the number of identity elements fitting into the tRNA structure.

6.
Microbiol Spectr ; 10(2): e0002522, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35416714

RESUMO

Acanthamoeba species are among the most ubiquitous protists that are widespread in soil and water and act as both a replicative niche and vectors for dispersal. They are the most important human intracellular pathogens, causing Acanthamoeba keratitis (AK) and severely damaging the human cornea. The sympatric lifestyle within the host and amoeba-resisting microorganisms (ARMs) promotes horizontal gene transfer (HGT). However, the genomic diversity of only A. castellanii and A. polyphaga has been widely studied, and the pathogenic mechanisms remain unknown. Thus, we examined 7 clinically pathogenic strains by comparative genomic, phylogenetic, and rhizome gene mosaicism analyses to explore amoeba-symbiont interactions that possibly contribute to pathogenesis. Genetic characterization and phylogenetic analysis showed differences in functional characteristics between the "open" state of T3 and T4 isolates, which may contribute to the differences in virulence and pathogenicity. Through comparative genomic analysis, we identified potential genes related to virulence, such as metalloprotease, laminin-binding protein, and HSP, that were specific to the genus Acanthamoeba. Then, analysis of putative sequence trafficking between Acanthamoeba and Pandoraviruses or Acanthamoeba castellanii medusaviruses provided the best hits with viral genes; among bacteria, Pseudomonas had the most significant numbers. The most parsimonious evolutionary scenarios were between Acanthamoeba and endosymbionts; nevertheless, in most cases, the scenarios are more complex. In addition, the differences in exchanged genes were limited to the same family. In brief, this study provided extensive data to suggest the existence of HGT between Acanthamoeba and ARMs, explaining the occurrence of diseases and challenging Darwin's concept of eukaryotic evolution. IMPORTANCE Acanthamoeba has the ability to cause serious blinding keratitis. Although the prevalence of this phenomenon has increased in recent years, our knowledge of the underlying opportunistic pathogenic mechanism maybe remains incomplete. In this study, we highlighted the importance of Pseudomonas in the pathogenesis pathway using comprehensive a whole genomics approach of clinical isolates. The horizontal gene transfer events help to explain how endosymbionts contribute Acanthamoeba to act as an opportunistic pathogen. Our study opens up several potential avenues for future research on the differences in pathogenicity and interactions among clinical strains.


Assuntos
Acanthamoeba , Transferência Genética Horizontal , Acanthamoeba/genética , Acanthamoeba/microbiologia , Genômica , Humanos , Filogenia , Pseudomonas , Fatores de Virulência/genética
7.
J Exp Bot ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35419601

RESUMO

Caleosins are lipid droplet and endoplasmic reticulum-associated proteins. To investigate their functions in oil accumulation, expression levels of caleosins in developing seeds of Arabidopsis thaliana were examined and four seed-expressed caleosins (CLO1, CLO2, CLO4 and CLO6) were identified. The four single mutants showed similar minor changes of fatty acid composition in seeds. Two double mutants (clo1 clo2 (CRISPR) and clo1×clo2 (crossing)) demonstrated distinct changes of fatty acid composition, 16-23% decrease of oil content and 10-13% decrease of seed weight. Moreover, a 40% decrease of oil content, further fatty acid changes and misshapen membrane of smaller lipid droplets were found in seeds of quadruple CLO RNAi lines. Notably, about 40% of quadruple CLO RNAi T1 seeds failed to germinate, and deformed embryos and seedlings were also found. Complementation experiments showed CLO1 rescued the phenotype of clo1 clo2. Overexpression of CLO1 in seedlings and BY2 cells increased triacylglycerol content up to 73.6%. Transcriptome analysis of clo1 clo2 developing seeds showed that expression levels of some genes related to lipid, embryo development, calcium signal and stress responses were affected. Taken together, our results suggest that the major seed-expressed caleosins have overlapping functions in oil accumulation and show pleiotropic effects on embryo development.

8.
ASAIO J ; 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412475

RESUMO

One of the cardinal features of any liver replacement therapy is the ability to remove accumulated metabolites. However, an unsolved problem is the low dialyzability of lipophilic toxins. This study aimed to explore whether bilirubin and bile acids removal can be increased by free fatty acid (FFA) displacement and its synergy with albumin dialysis. First, we found that the protein binding of both bilirubin and bile acids decreased significantly with increasing FFA concentrations when co-incubated directly. Then, in vitro dialysis showed that fatty acid mixtures infusion prefilter effectively increased the fractional removals of bilirubin and bile acids, showing higher efficiency compared with albumin-based hemodialysis (HD); in vivo dialysis in liver failure rats showed that lipid emulsion administration resulted in higher reduction ratios and more total solute removals for bilirubin and bile acids after 4 h HD compared with control, which were also superior to albumin-based HD. Finally, the highest dialysis efficacy was always observed by their synergy whether in vitro or in vivo. These findings highlight that FFA displacement-based HD could efficiently improve the dialytic removal of bilirubin and bile acids, which might even be more efficient than albumin-based HD. Their synergy may represent a promising strategy to maximize the removal of circulating bilirubin and bile acids accumulated in liver failure.

9.
Int J Biol Macromol ; 206: 633-641, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35247422

RESUMO

Pesticide compounding technology for disease and pest control emerges as an effective way to increase the effectiveness of pesticides while reducing pesticides resistance. Nanomaterials and encapsulation technology have offered a new insight into preparing efficient pesticide formulations, especially constructing a co-delivery nanoparticle for synergistic pesticides. In this study, a dinotefuran/avermectin co-delivery nanoparticles (DACNPs) against pear tree pests with polylactic acid (PLA) as the wall material were constructed by double-emulsion method combined with high-pressure homogenization technique. The drug content of the DACNPs was 39.1% with an average size of 245.7 ± 4.2 nm and the mean polymer dispersity index (PDI) value was 0.123. The DACNPs showed high foliar retention and good spread performance on target leaves due to the nanoscale effect. The obtained DACNPs showed a better control effect on Grapholitha molesta Busck and Psylla chinensis Yang et Li compared with the commercial formulations, which could significantly prolong the effective duration and enhance the bioactivity with lower amounts and application frequency of pesticides. This study may provide new insights into developing novel pesticide formulations to improve the utilization rate of pesticides, reduce environmental pollution and minimize the cost of farming.


Assuntos
Nanopartículas , Praguicidas , Pyrus , Guanidinas , Ivermectina/análogos & derivados , Neonicotinoides , Nitrocompostos , Praguicidas/farmacologia , Poliésteres , Árvores
10.
Biochim Biophys Acta Rev Cancer ; 1877(3): 188720, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35304295

RESUMO

Unsatisfied clinical outcome drives to better understand hepatic carcinogenesis, microenvironment and escape of immune surveillance in hepatocellular carcinoma (HCC). Single cell RNA sequencing (scRNA-Seq) has generated enormous data to pinpoint pathophysiologic alterations in tumor microenvironment (TME) or trace lineage development in cancer stem cells (CSCs), circulating tumor cells (CTCs), and subsets of immune cells, such as exhausting T cells, tumor-associated macrophages (TAMs), dendritic cells or other lineages. New insights have significantly advanced current understanding in progression, poor responses to molecular-targeted therapeutics or immune checkpoint inhibitors, metastasis in both basic research and clinical practice. The present review intends to cover a basic workflow of the scRNA-seq technology, existing limitations and improvement areas. Moreover, in-depth understanding in TME, exhausting T cells, CSCs, CTCs, tumor-associated macrophages, dendritic cells in HCC facilitates implementation of personalized and precise therapy in an era of availability with an array of systemic regimens.

11.
Curr Gene Ther ; 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264092

RESUMO

BACKGROUND: Osteoarthritis (OA) is the predominant threaten to the health of the elderly, and it is crucial to understand the molecular pathegenetic mechanisms involved in it. This study aims to investigate the role of a well-studied cancer-related long noncoding RNA (lncRNA)-POU3F3 in OA and its implicated molecular mechanisms. METHOD: The expression of POU3F3 and miR-29a-3p was examined in osteoarthritis patients, destabilization of the medial meniscus (DMM) mouse OA model, and IL- 1ß induced chondrocytes cell OA model by quantitative real-time PCR. The interaction between POU3F3, miR-29a-3p and transcription factor forkhead box O3 (FOXO3) was verified by via dual-luciferase reporter analysis and RNA immunoprecipitation analyses. Cell proliferation and apoptosis were evaluated by cell viability assay and flow cytometry, respectively. Cartilage extracellular matrix (ECM) degradation were investigated with ELISA and western blotting. In addition, the in vivo regulation of POU3F3 in OA was verified by intra-articular injection of lentivirus overexpression POU3F31 in mice models. RESULTS: The expression level of POU3F3 was decreased in OA patients/animal cartilage tissues and IL-1ß-stimulated in vitro chondrocyte model. POU3F3 overexpression inhibited IL-1ß-induced injury of chondrocytes, enhancing cell viability, suppressing apoptosis and inflammatory cytokine secretion, rescuing metabolic dysfunction, and restrained autophagy in vitro. Mechanistically, Luciferase reporter and RNA immunoprecipitation (RIP) assays indicated that miR-29a-3p could directly bind to POU3F3 and FOXO3 was a target gene of miR-29a-3p. Functional rescue assays confirmed this POU3F3/miR-29a-3p/FOXO3 axis in chondrocytes during OA occurrence. Furthermore, intra-articularly delivery of lentivirus containing POU3F3 alleviates the damage in mouse OA model in vivo. CONCLUSION: In conclusion, this work highlights the function of POU3F3/miR-29a-3p/FOXO3 axis in OA pathogenesis, suggesting this axis as a potential progression of OA [12-15]. These studies indicate the potential contribution of lncRNAs in the development of OA and a promising target for disease diagnosis and treatment.

12.
Front Vet Sci ; 9: 840442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252427

RESUMO

Chlortetracycline is a broad-spectrum antibiotic used as an oral medication in ruminants. However, this antibiotic affects the rumen microbial population, thereby upsetting the normal microbiota of ruminants. This study determined whether our newly developed chlortetracycline rumen-protected granules are relatively harmless to rumen microorganisms while effective against lamb E. coli diarrhea. We used a qPCR assay to quantify selected rumen microorganisms from lambs treated with or without oral chlortetracycline. We also assessed bacterial diversity in the rumen by 16S rRNA gene sequencing. Lambs were divided into three groups: one group given with oral chlortetracycline granules for 7 days; one group with chlortetracycline premix; and one without treatment. Rumen fluid was collected on 0 d, 7 d, and 14 d of the experiment. In the therapeutic effect trial, cases of naturally E. coli-infected lamb with diarrhea were selected and divided into low, medium, and high dose groups of granules, premix, infection control, and healthy control groups. Treatments were continuously administered for 7 days, and animals were observed for 14 days after drug withdrawal to score and evaluate the treatment effect. Results of qPCR and 16S rRNA gene sequencing showed that the granules could diminish the impact of chlortetracycline on rumen microorganisms compared with the premix. The diarrhea therapeutic effect trial showed that the oral administration of the chlortetracycline rumen-protected granules at the dose of 30 mg/kg·bw/d for 7 days could effectively treat lamb diarrhea caused by E. coli. In conclusion, we provide a new drug preparation of chlortetracycline that can diminish the effect on the rumen microbiota while treating diarrhea caused by E. coli.

14.
Int J Mol Sci ; 23(6)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35328783

RESUMO

Diabetes is a chronic metabolic disease characterized by lack of insulin in the body leading to failure of blood glucose regulation. Diabetes patients usually need frequent insulin injections to maintain normal blood glucose levels, which is a painful administration manner. Long-term drug injection brings great physical and psychological burden to diabetic patients. In order to improve the adaptability of patients to use insulin and reduce the pain caused by injection, the development of oral insulin formulations is currently a hot and difficult topic in the field of medicine and pharmacy. Thus, oral insulin delivery is a promising and convenient administration method to relieve the patients. However, insulin as a peptide drug is prone to be degraded by digestive enzymes. In addition, insulin has strong hydrophilicity and large molecular weight and extremely low oral bioavailability. To solve these problems in clinical practice, the oral insulin delivery nanosystems were designed and constructed by rational combination of various nanomaterials and nanotechnology. Such oral nanosystems have the advantages of strong adaptability, small size, convenient processing, long-lasting pharmaceutical activity, and drug controlled-release, so it can effectively improve the oral bioavailability and efficacy of insulin. This review summarizes the basic principles and recent progress in oral delivery nanosystems for insulin, including physiological absorption barrier of oral insulin and the development of materials to nanostructures for oral insulin delivery nanosystems.


Assuntos
Diabetes Mellitus , Nanoestruturas , Administração Oral , Glicemia , Diabetes Mellitus/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Insulina/uso terapêutico , Insulina Regular Humana/uso terapêutico , Preparações Farmacêuticas
15.
ACS Synth Biol ; 11(4): 1588-1599, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35290032

RESUMO

Synthetic genomics will advance our understanding of life and allow us to rebuild the genomes of industrial microorganisms for enhancing performances. Corynebacterium glutamicum, a Gram-positive bacterium, is an important industrial workhorse. However, its genome synthesis is impeded by the low efficiencies in DNA delivery and in genomic recombination/replacement. In the present study, we describe a genomic iterative replacement system based on RecET recombination for C. glutamicum, involving the successive integration of up to 10 kb DNA fragments obtained in vitro, and the transformants are selected by the alternative use of kanR and speR selectable markers. As a proof of concept, we systematically redesigned and replaced a 54.3 kb wild-type sequence of C. glutamicumATCC13032 with its 55.1 kb synthetic counterpart with several novel features, including decoupled genes, the standard PCRTags, and 20 loxPsym sites, which was for the first time incorporated into a bacterial genome. The resulting strain semi-synCG-A1 had a phenotype and fitness similar to the wild-type strain under various stress conditions. The stability of the synthetic genome region faithfully maintained over 100 generations of nonselective growth. Genomic deletions, inversions, and translocations occurred in the synthetic genome region upon induction of synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE), revealing potential genetic flexibility for C. glutamicum. This strategy can be used for the synthesis of a larger region of the genome and facilitate the endeavors for metabolic engineering and synthetic biology of C. glutamicum.


Assuntos
Corynebacterium glutamicum , Corynebacterium glutamicum/metabolismo , Genoma Bacteriano/genética , Genômica , Engenharia Metabólica/métodos , Biologia Sintética
16.
ACS Synth Biol ; 11(3): 1167-1177, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35175748

RESUMO

For the biomedical application of engineered bacteria, strictly regulating the function of engineered bacteria has always been the goal pursued. However, the existing regulation methods do not meet the needs of the in vivo application of engineered bacteria. Therefore, the exploration of the precise regulation of engineered bacteria is necessary. Herein, heat-sensitive engineered bacteria that can respond to thermal stimuli within 30 min were constructed, and the precise control of functions was verified in the intestines of various model organisms (including C. elegans, bees, and mice). Subsequently, heat-sensitive engineered bacteria were shown to colonize the mouse tumor microenvironment. Finally, thermal stimulation was proven to control engineered bacteria to produce the therapeutic protein tumor necrosis factor α (TNF-α) in the tumor. After three heat stimulation treatments, the growth of the tumor was significantly inhibited, suggesting that heat can be used as a strategy to precisely control engineered bacteria in vivo.


Assuntos
Bactérias , Neoplasias , Animais , Bactérias/genética , Caenorhabditis elegans , Temperatura Alta , Camundongos , Microrganismos Geneticamente Modificados , Neoplasias/terapia , Microambiente Tumoral , Fator de Necrose Tumoral alfa/biossíntese
17.
Artigo em Inglês | MEDLINE | ID: mdl-35124186

RESUMO

Basal metabolic rate (BMR) has been shown to be a highly phenotypic flexibility trait within species. A significant proportion of an individual's energy budget is accounted for by BMR, hence among-individual variation in this trait may affect other energetic processes, as well as fitness. In this study, we measured BMR, organ mass, mitochondrial respiration capacities and cytochrome c oxidase (COX) activities in muscle and liver and circulating levels of plasma triiodothyronine (T3) in Chinese bulbuls (Pycnonotus sinensis) and Eurasian tree sparrows (Passer montanus). Our results showed that heart and kidney mass was positively correlated with BMR in Chinese bulbuls, whereas liver and kidney mass was positively correlated with BMR in Eurasian tree sparrows. Regarding metabolic biochemical markers of tissues, state 4 respiration and COX activity in the muscles of the Chinese bulbuls was correlated with BMR, while state 4 respiration in the muscle and liver was correlated with BMR in Eurasian tree sparrows. T3 was significantly and positively correlated with BMR in Chinese bulbuls and Eurasian tree sparrows. Consistent with the above results, our findings suggest that T3 levels play an important role in modulating BMR in Chinese bulbuls and Eurasian tree sparrows. Moreover, individual variation in BMR can be explained partly by morphological and physiological mechanisms.


Assuntos
Metabolismo Basal , Pardais , Animais , Fígado , Músculos , Tri-Iodotironina
18.
Entropy (Basel) ; 24(2)2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35205573

RESUMO

Redundant manipulators are widely used in fields such as human-robot collaboration due to their good flexibility. To ensure efficiency and safety, the manipulator is required to avoid obstacles while tracking a desired trajectory in many tasks. Conventional methods for obstacle avoidance of redundant manipulators may encounter joint singularity or exceed joint position limits while tracking the desired trajectory. By integrating deep reinforcement learning into the gradient projection method, a reactive obstacle avoidance method for redundant manipulators is proposed. We establish a general DRL framework for obstacle avoidance, and then a reinforcement learning agent is applied to learn motion in the null space of the redundant manipulator Jacobian matrix. The reward function of reinforcement learning is redesigned to handle multiple constraints automatically. Specifically, the manipulability index is introduced into the reward function, and thus the manipulator can maintain high manipulability to avoid joint singularity while executing tasks. To show the effectiveness of the proposed method, the simulation of 4 degrees of planar manipulator freedom is given. Compared with the gradient projection method, the proposed method outperforms in a success rate of obstacles avoidance, average manipulability, and time efficiency.

19.
J Phys Chem Lett ; 13(6): 1563-1570, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35138107

RESUMO

For the direct luminescence of triplet excitons, different mechanisms have been proposed for realizing pure organic room-temperature phosphorescence (RTP). To further verify the mechanism of folding-induced spin-orbit coupling (SOC) enhancement, two analogues of thianthrene (TA) were introduced by gradually replacing the sulfur atom with an oxygen atom for a systematical comparison, corresponding to phenoxathiine (PX) and dioxins (DX) molecules with increasing folding dihedral angles (or decreasing degrees of folding). Photophysical measurements show an obviously enhanced RTP efficiency from DX and PX to TA, which is consistent with their greatly enhanced SOC with a decrease in folding dihedral angle. The folding angle-dependent SOC calculations for each molecule reveal that this enhanced RTP is dominated by folding-induced SOC enhancement, in contrast with the negligible heavy-atom effect from oxygen to sulfur. This work further validates the rationality of the folding-induced SOC enhancement mechanism, which provides an innovative molecular design strategy for developing efficient pure organic RTP materials using folding structures.

20.
Biochem Biophys Res Commun ; 599: 148-155, 2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-35182941

RESUMO

Actin-like 6A (ACTL6A) is a core subunit of the SWI/SNF chromatin remodeling complex and is highly expressed in several types of human cancers including glioblastoma. Recent studies verified that ACTL6A regulates the proliferation, differentiation, and migration of cancer cells. In this study, we identified ACTL6A as an important regulator of DNA replication. ACTL6A knockdown could impair the DNA replication initiation in glioblastoma cells. The regulation of DNA replication by ACTL6A was mediated through regulating the expression of the CDC45-MCM-GINS (CMG) complex genes. Further investigation revealed that ACTL6A transcriptionally regulates MCM5 expression. Furthermore, ACTL6A knockdown induced DNA damage and diminished the activity of the ATR-Chk1 pathway, which ultimately led glioblastoma cells to apoptosis and death. Taken together, our findings highlight the critical role of ACTL6A in DNA replication and ATR-Chk1 pathway, and reveal a potential target for therapeutic intervention in glioblastoma.


Assuntos
Actinas/genética , Apoptose/genética , Proteínas Cromossômicas não Histona/genética , Replicação do DNA , Proteínas de Ligação a DNA/genética , Glioblastoma/genética , Glioblastoma/patologia , Actinas/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Quinase 1 do Ponto de Checagem/genética , Quinase 1 do Ponto de Checagem/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Transdução de Sinais/fisiologia
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