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1.
J Colloid Interface Sci ; 607(Pt 1): 881-889, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34536941

RESUMO

The silicon coated Carbon nanotubes (CNTs) nanocomposite (CNTs@Si) with a shell structure was successfully synthesized by a simple chemical vapor deposition (CVD) method. In this work, the CNTs@Si is not only introduced as a structural material providing oxidation performance, but also as an extremely effective electromagnetic wave (EMW) absorption nanocomposite. Dielectric characteristics EMW absorption properties within the frequency range of 2-18 GHz of CNTs@Si were studied, and the oxidation resistance of CNTs@Si was characterized. Due to the dense space conductive network formed by CNTs, the EMW absorbing properties of CNTs@Si nanocomposite features excellent electromagnetic wave absorption capacity at a filling amount of 1%. The maximum reflection loss (RL) reaches -61.57 dB at the thickness of 1.8 mm, and a wide effective absorption bandwidth (EAB, RL < -10 dB) of 2.88 GHz is achieved. The obtained CNTs@Si core-shell nanocomposites exhibit excellent antioxidant performance and absorbing performance due to silicon bridging. Efficient electromagnetic wave absorption and excellent oxidation resistance of CNTs@Si can be regarded as a brand-new competitive candidate for EMW absorption materials in harsh environment.

2.
Curr Neurovasc Res ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34758715

RESUMO

OBJECTIVE: To determine whether the administration of intravenous alteplase would be beneficial or futile to patients with acute ischemic stroke caused by large vessel occlusion (LVO) before endovascular treatment (EVT), we conducted this study to determine the relationship between Hounsfield units (HU) in non-contrast computed tomography (NCCT) and recanalization by alteplase. METHODS: We performed a retrospective analysis of patients with acute ischemic stroke caused by LVO received intravenous thrombolysis (IVT) or followed by EVT at our center during November 2016 and October 2020. The clinical characteristics and imaging features of patients who achieved recanalization after IVT, and those who did not, were compared. RESULTS: Forty-three eligible patients were enrolled; 12 achieved recanalization by IVT. Baseline clinical characteristics did not differ between patients of the recanalization and non-recanalization groups. HU in the NCCT were estimated and statistically significant maximum and mean values of the ipsilateral middle cerebral artery (MCA) were found between the groups (P< 0.05). The results hint that patients in the non-recanalization group have a higher rHU and δHU value of the ipsilateral MCA compared with recanalization group (P< 0.05). With regards the receiver operator characteristic (ROC) curve, we demonstrated that a high HU value of the ipsilateral MCA could be a predictor for non-recanalization by IVT. CONCLUSION: Patients suffering LVO stroke are less likely to obtain recanalization by IVT with a high HU value of the ipsilateral MCA. It is feasible to screen patients with LVO using HU for direct EVT.

3.
Hepatology ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34662438

RESUMO

BACKGROUND & AIMS: Ischemia reperfusion (I/R) injury is an inevitable complication of liver transplantation and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain largely unknown in hepatic I/R injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-Acetylgalactosaminyltransferase-4 (GALNT4), in hepatic I/R injury. APPROACH & RESULTS: Via an RNA-seq data-based correlation analysis, we found a close correlation between GALNT4 expression and hepatic I/R-related molecular events in murine model. The mRNA and protein expression of GALNT4 were markedly upregulated upon reperfusion surgery in both clinical samples from subjects underwent liver transplantation and mouse model. We found that GALNT4 deficiency significantly exacerbated I/R-induced liver damage, inflammation and cell death, whereas GALNT4 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration clarified that GALNT4 directly binds to the apoptosis signal-regulating kinase1 (ASK1) to inhibit its N-terminal dimerization and subsequent phosphorylation, leading to a robust inactivation of the downstream c-Jun N-terminal kinase (JNK) / p38 and nuclear factor kappa B (NF-κB) signalling. Intriguingly, the inhibitory capacity of GALNT4 on ASK1 activation is independent of its glycosyltransferase activity. CONCLUSIONS: GALNT4 represents a promising therapeutic target for liver I/R injury and improve liver surgery prognosis by inactivating ASK1-JNK/p38 signalling pathway.

4.
Mol Plant ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34715392

RESUMO

As one of the most important crops in the world, rice (Oryza sativa) is a model plant for metabolome research. Although many studies have focused on the analysis of specific tissues, the changes in metabolite abundance across the entire life cycle have not yet been determined. In this study, combining both targeted and nontargeted metabolite profiling methods, a total of 825 annotated metabolites were quantified in rice samples from different tissues covering the entire life cycle. The contents of metabolites in different tissues of rice were significantly different, with various metabolites accumulating in the plumule and radicle during seed germination. Combining these data with transcriptome data obtained from the same time period, we constructed the Rice Metabolic Regulation Network. The metabolites and co-expressed genes were further divided into 12 clusters according to their accumulation patterns, with members within each cluster displaying a uniform and clear pattern of abundance across development. Using this dataset, we established a comprehensive metabolic profile of the rice life cycle and used two independent strategies to identify novel transcription factors-namely the use of known regulatory genes as bait to screen for new networks underlying lignin metabolism and the unbiased identification of new glycerophospholipid metabolism regulators on the basis of tissue specificity. This study thus demonstrates how guilt-by-association analysis of metabolome and transcriptome data spanning the entire life cycle in cereal crops provides novel resources and tools to aid in understanding the mechanisms underlying important agronomic traits.

5.
Macromol Rapid Commun ; 42(23): e2100499, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34480782

RESUMO

Stimulus-responsive hydrogels are of great significance in soft robotics, wearable electronic devices, and sensors. Near-infrared (NIR) light is considered an ideal stimulus as it can trigger the response behavior remotely and precisely. In this work, a smart flexible stimuli-responsive hydrogel with excellent photothermal property and decent conductivity are prepared by incorporating MXene nanosheets into the physically cross-linked poly(N-isopropyl acrylamide) hydrogel matrix. Because of outstanding photothermal effect and dispersion of MXene, the composite hydrogel exhibits rapid photothermal responsiveness and excellent photothermal stability under the NIR irradiation. Furthermore, the anisotropic bilayer hydrogel actuator shows fast and controllable light-driven bending behavior, which can be used as a light-controlled soft manipulator. Meanwhile, the hydrogel sensor exhibits cycling stability and good durability in detecting various deformation and real-time human activities. Therefore, the present study involving the fabrication of MXene nanocomposite hydrogels for potential applications in remotely controlled actuator and wearable electronic device provides a new method for the development of photothermal responsive conductive hydrogels.

6.
ACS Appl Mater Interfaces ; 13(36): 43426-43437, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34491715

RESUMO

The fabrication of a single polymer network that exhibits a good reversible two-way shape memory effect (2W-SME), can be formed into arbitrarily complex three-dimensional (3D) shapes, and is recyclable remains a challenge. Herein, we design and fabricate poly(thiourethane) (PTU) networks with an excellent thermadapt reversible 2W-SME, arbitrary reconfigurability, and good recyclability via the synergistic effects of multiple dynamic covalent bonds (i.e., ester, urethane, and thiourethane bonds). The PTU samples with good mechanical performance simultaneously demonstrate a maximum tensile stress of 29.7 ± 1.1 MPa and a high strain of 474.8 ± 7.5%. In addition, the fraction of reversible strain of the PTU with 20 wt % hard segment reaches 22.4% during the reversible 2W-SME, where the fraction of reversible strain is enhanced by self-nucleated crystallization of the PTU. A sample with arbitrarily complex permanent 3D shapes can be realized via the solid-state plasticity, and that sample also exhibits excellent reversible 2W-SME. A smart light-responsive actuator with a double control switch is fabricated using a reversible two-way shape memory PTU/MXene film. In addition, the PTU networks are de-cross-linked by alcohol solvolysis, enabling the recovery of monomers and the realization of recyclability. Therefore, the present study involving the design and fabrication of a PTU network for potential applications in intelligent actuators and multifunctional shape-shifting devices provides a new strategy for the development of thermadapt reversible two-way shape memory polymers.

7.
IEEE Trans Cybern ; PP2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520384

RESUMO

Generating various goal-oriented movements via the flexible muscle model of the musculoskeletal system as fast and accurately as possible is a pressing problem, which is also the basis of most human adaptive behaviors, such as reaching, catching, interception, and pointing. This article focuses on the adaptive motion generation of fast goal-oriented motion on the musculoskeletal system by implementing the speed-accuracy tradeoff (SAT) in a hierarchical motion learning framework. First, we introduce Fitts' Law into the modified basal ganglia circuit-inspired iterative decision-making model for achieving dynamic and adaptive decision making. Then, as a time constraint, the decision is decomposed into a series of supervised terms by the proposed striatal FSI-SPN interneuron circuit-inspired velocity modulator to implement the tradeoff smoothly on the musculoskeletal system. Finally, an improved policy gradient algorithm is suggested to generate the muscle excitations of the modulated motion via the proposed muscle co-contraction policy, which promotes general cooperation between flexor and extensor muscles. In experiments, a redundant musculoskeletal arm model is trained to perform the adaptive quick pointing movements. By combining the muscle co-contraction policy with SAT, our algorithm shows the most efficient training and the best performance in the adaptive motion generation among the other three popular reinforcement learning algorithms on the musculoskeletal model.

8.
Front Immunol ; 12: 707191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349766

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable clinical efficacy in treatment of many malignancies especially for B-cell hematologic malignancies. However, the application of CAR-T cells is hampered by potentially adverse events, of which cytokine release syndrome (CRS) is one of the severest and the most studied. Local cytokine-release syndrome (L-CRS) at particular parts of the body has been reported once in a while in B-cell lymphoma or other compartmental tumors. The underlying mechanism of L-CRS is not well understood and the existing reports attempting to illustrate it only involve compartmental tumors, some of which even indicated L-CRS only happens in compartmental tumors. Acute lymphoblastic leukemia (ALL) is systemic and our center treated a B-cell ALL patient who exhibited life threatening dyspnea, L-CRS was under suspicion and the patient was successfully rescued with treatment algorithm of CRS. The case is the firstly reported L-CRS related to systemic malignancies and we tentatively propose a model to illustrate the occurrence and development of L-CRS of systemic malignancies inspired by the case and literature, with emphasis on the new recognition of L-CRS.

9.
IEEE Trans Cybern ; PP2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34403350

RESUMO

This article presents a structure constraint matrix factorization framework for different behavior segmentation of the human behavior sequential data. This framework is based on the structural information of the behavior continuity and the high similarity between neighboring frames. Due to the high similarity and high dimensionality of human behavior data, the high-precision segmentation of human behavior is hard to achieve from the perspective of application and academia. By making the behavior continuity hypothesis, first, the effective constraint regular terms are constructed. Subsequently, the clustering framework based on constrained non-negative matrix factorization is established. Finally, the segmentation result can be obtained by using the spectral clustering and graph segmentation algorithm. For illustration, the proposed framework is applied to the Weiz dataset, Keck dataset, mo_86 dataset, and mo_86_9 dataset. Empirical experiments on several public human behavior datasets demonstrate that the structure constraint matrix factorization framework can automatically segment human behavior sequences. Compared to the classical algorithm, the proposed framework can ensure consistent segmentation of sequential points within behavior actions and provide better performance in accuracy.

10.
Front Neurosci ; 15: 709684, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354569

RESUMO

Neurogenesis is a complex process that depends on the delicate regulation of spatial and temporal gene expression. In our previous study, we found that transcribed ultra-conserved regions (T-UCRs), a class of long non-coding RNAs that contain UCRs, are expressed in the developing nervous systems of mice, rhesus monkeys, and humans. In this study, we first detected the full-length sequence of T-uc.189, revealing that it was mainly concentrated in the ventricular zone (VZ) and that its expression decreased as the brain matured. Moreover, we demonstrated that knockdown of T-uc.189 inhibited neurogenesis. In addition, we found that T-uc.189 positively regulated the expression of serine-arginine-rich splicing factor 3 (Srsf3). Taken together, our results are the first to demonstrate that T-uc.189 regulates the expression of Srsf3 to maintain normal neurogenesis during cortical development.

11.
Hepatology ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435375

RESUMO

BACKGROUND & AIMS: Although the prevalence of nonalcoholic fatty liver disease (NAFLD) has risen dramatically to 25% of the adult population worldwide, there are as yet no approved pharmacological interventions for the disease due to uncertainty about the underlying molecular mechanisms. It is known that mitochondrial dysfunction is an important factor in the development of NAFLD. Mitochondrial antiviral signaling protein (MAVS) is a critical signaling adaptor for host defenses against viral infection. However, the role of MAVS in mitochondrial metabolism during NAFLD progression remains largely unknown. APPROACH & RESULTS: Based on expression analysis, we identified a marked downregulation of MAVS in hepatocytes during NAFLD progression. By employing MAVS global knockout and hepatocyte-specific MAVS knockout mice, we found that MAVS is protective against diet-induced NAFLD. MAVS deficiency induces extensive mitochondrial dysfunction during NAFLD pathogenesis which was confirmed as impaired mitochondrial respiratory capacity and membrane potential. Metabolomics data also showed the extensive metabolic disorders after MAVS deletion. Mechanistically, MAVS interacts with the N-terminal stretch of voltage-dependent anion channel 2 (VDAC2), which is required for the ability of MAVS to influence mitochondrial function and hepatic steatosis. CONCLUSIONS: In hepatocytes, MAVS plays an important role in protecting against NAFLD by helping to regulate healthy mitochondrial function. These findings provide new insights regarding the metabolic importance of conventional immune regulators and support the possibility that targeting MAVS may represent a new avenue for treating NAFLD.

12.
Sci Total Environ ; 799: 149482, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34365257

RESUMO

Exogenous fertilization could efficiently improve grassland productivity and promote grassland restoration. Increasing fertilization may profoundly affect community stability, whereas the underlying compensatory dynamics among functional groups in regulating grassland stability remain unclear. Three different grasslands, annuals forb (AF) community, perennial grass (PG) community and perennial forb (PF) community, on semiarid Loess Plateau were selected. We designed a 3-year split-plot experiment (main-plot: 0, 25, 50, and 100 kg N ha-1 yr-1; subplot: 0, 20, 40 and 80 kg P2O5 ha-1 yr-1) to explore how N and P addition affects community stability and its relationship with species richness, species asynchrony and functional group stability. Temporal stability differed largely between functional groups under N and P addition, perennial forbs or grasses had higher stability than perennial legumes or annuals and biennials. Decreased stability of PG and PF communities was primarily due to reduced species asynchrony under N addition alone, while it attributed to increased dominance of perennial legumes after P addition alone. 50 and 100 kg N ha-1 yr-1 combined with P addition significantly increased dominance of annuals and biennials, but decreased stability of annuals and biennials, which caused significant declines in stability of the three communities. Significant species richness decline induced by N and P addition only occurred in AF community, which suppressed AF community stability through reducing species asynchrony. AF community stability was regulated by additively negative effect of diversity decline and decreased annuals and biennials stability. Whereas, in PG and PF communities, nutrient-induced changes of functional groups stability were the main driver of community stability rather than diversity. Our study highlights the role of functional group composition and dynamics in regulating the effects of diversity on community stability and rational N and P combined addition was essential for conserving stability of different grasslands on semiarid Loess Plateau.


Assuntos
Fabaceae , Pradaria , Biodiversidade , Poaceae
13.
Environ Sci Pollut Res Int ; 28(47): 67788-67799, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34264494

RESUMO

Soil aggregates display a significant influence on the bioavailability of heavy metals in soil. In this study, we conducted a field experiment in the main producing area of Ligusticum striatum DC. to explore the effects of the amendments on cadmium (Cd) distribution in soil aggregates and plant growth. L. striatum was planted in natural Cd-polluted soils added with mixed amendments, composed of heavy/light calcium carbonate (Type 1/Type 2 amendments), calcium-bentonite, potassium dihydrogen phosphate, biochar, sodium silicate, and attapulgite, with the application rate of 0.5 t ha-1, 1.5 t ha-1, and 5.0 t ha-1. The results demonstrated that the application of the amendments promoted the formation of soil macroaggregates (250-2000 µm and >2000 µm) and, altered soil Cd distribution among aggregates fractions by translocating Cd from macroaggregates into small one (microaggregate; <250 µm). Soil amendments addition greatly alleviated the phytotoxic effects of Cd on plants and promoted the biomass of the rhizome of L. striatum by 14.38-53.47%. Based on the structural equation modeling, the decrease of available Cd in the fraction of large macroaggregates greatly contributed to the less accumulation of Cd in plants (r = 0.70; p < 0.05). In general, the amendments inhibited the plant Cd accumulation by re-distribution of Cd among soil aggregates and, improved the plant growth by supplying available nutrients.

14.
Opt Express ; 29(13): 19853-19861, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34266087

RESUMO

Terahertz emission by ultrafast excitation of semiconductor/metal interfaces was found strongly enhanced by plasmon resonance. Here, a three-dimensional nanoporous gold (NPG) was used to form semiconductor/metal compound with cadmium telluride (CdTe). We investigated the specific impact of surface plasmon from randomly nanoporous structure in the ultrafast optoelectronic response for THz generation, and observed a THz amplitude enhancement around an order of magnitude from CdTe on NPG compared to that from CdTe on silicon. Moreover, the plasmon enhancement for THz emission from NPG is stronger than that from gold film, indicating that randomly nanoporous structure is also effective for plasmonic enhancement in THz band.

15.
Hepatology ; 74(4): 2133-2153, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34133792

RESUMO

BACKGROUND AND AIMS: Hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, causes a large proportion of early graft failure and organ rejection cases. The identification of key regulators of hepatic I/R injury may provide potential strategies to clinically improve the prognosis of liver surgery. Here, we aimed to identify the role of tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in hepatic I/R injury and further reveal its immanent mechanisms. APPROACH AND RESULTS: In the present study, we found that hepatocyte TNIP3 was markedly up-regulated in livers of both persons and mice subjected to I/R surgery. Hepatocyte-specific Tnip3 overexpression effectively attenuated I/R-induced liver necrosis and inflammation, but improved cell proliferation in mice, whereas TNIP3 ablation largely aggravated liver injury. This inhibitory effect of TNIP3 on hepatic I/R injury was found to be dependent on significant activation of the Hippo-YAP signaling pathway. Mechanistically, TNIP3 was found to directly interact with large tumor suppressor 2 (LATS2) and promote neuronal precursor cell-expressed developmentally down-regulated 4-mediated LATS2 ubiquitination, leading to decreased Yes-associated protein (YAP) phosphorylation at serine 112 and the activated transcription of factors downstream of YAP. Notably, adeno-associated virus delivered TNIP3 expression in the liver substantially blocked I/R injury in mice. CONCLUSIONS: TNIP3 is a regulator of hepatic I/R injury that alleviates cell death and inflammation by assisting ubiquitination and degradation of LATS2 and the resultant YAP activation.TNIP3 represents a promising therapeutic target for hepatic I/R injury to improve the prognosis of liver surgery.

16.
Mol Carcinog ; 60(8): 556-566, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34061408

RESUMO

The epithelial-mesenchymal transition (EMT) is a pivotal step involved in cancer recurrence and metastasis. In addition, the activation of the EMT program can induce a cancer stem cell (CSC)-like phenotype and programmed death-ligand 1 (PD-L1) expression in head and neck squamous cell carcinoma (HNSCC). The CMTM family has reported as an important regulator in this process. Here, we investigated the role of CMTM4 in HNSCC. We indicated that CMTM4 was overexpressed in human and mouse HNSCC samples and in HNSCC cell lines by immunohistochemistry and Western blot. A high expression level of CMTM4 was correlated with advanced lymph node metastasis and a negative prognosis. CMTM4-knockdown by small interfering RNA downregulated the EMT process and inhibited the migration and invasion abilities of tumor cells. Moreover, knockdown of CMTM4 decreased CSC-associated markers via the protein kinase B pathway. Notably, CMTM4-knockdown inhibited the expression of interferon-γ induced PD-L1 in HNSCC cells. A positive correlation was found between CMTM4 expression and CD8+ and PD-1+ cell density in the stroma. Our findings indicated that CMTM4 may play an important role in regulating EMT/CSC phenotypes and PD-L1 expression. This study may reinforce the interest in CMTM4 as a potential target for the prognosis and treatment of HNSCC.


Assuntos
Antígeno B7-H1/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas com Domínio MARVEL/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Metástase Linfática , Proteínas com Domínio MARVEL/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Microambiente Tumoral/genética
17.
Small ; 17(23): e2101301, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33939883

RESUMO

Achieving uniform lithium (Li) deposition is the key to tackle uncontrollable dendrite growth, which hinders the application of Li metal anodes. In this study, molten Li is thermally injected into a 3D framework by growing lithiophilic CoO nanosheets on Cu foam (CF). The CoO layer grown on the CF surface physically adsorbs molten Li, which makes it possible to spontaneously wet the framework. The morphology of CoO nanosheets does not change during the Li injection process and formed a multi-level structure with the CF, which is difficult to be achieved previously, as most lithiophilic oxides undergo serious chemical changes due to chemical reaction with Li and cannot provide a stable submicron structure for the subsequent Li stripping/plating process. The super-assembled multi-level structure provides abundant Li nucleation sites and electrolyte/electrode contact areas for rapid charge transfer in the composite anode. Therefore, the prolonged lifespan of symmetrical cells for 300 cycles at 10 and 10 mAh cm-2 with lower polarization is achieved, which further renders the LiFePO4 and Li4 Ti5 O12 based full cells with improved capacity retention up to 87.3% and 80.1% after 500 cycles at 1 C. These results suggest that the composite anode has a great application prospect.

18.
Mol Immunol ; 135: 294-303, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33957479

RESUMO

Increasing evidence suggests that endoplasmic reticulum (ER) stress activates several pro-inflammatory signaling pathways in many diseases, including acute lung injury (ALI). We have reported that blocking triggering receptor expressed on myeloid cells 1 (TREM-1) protects against ALI by suppressing pulmonary inflammation in mice with ALI induced by lipopolysaccharides (LPS). However, the molecular mechanism underlying the TREM-1-induced pro-inflammatory microenvironment in macrophages remains unclearly. Herein, we aimed to determine whether TREM-1 regulates the inflammatory responses induced by LPS associated with ER stress activation. We found that the activation of TREM-1 by a monoclonal agonist antibody (anti-TREM-1) increased the mRNA and protein levels of IL-1ß, TNF-α, and IL-6 in primary macrophages. Treatment of the anti-TREM-1 antibody increased the expression of ER stress markers (ATF6, PERK, IRE-1α, and XBP-1s) in primary macrophages. While pretreatment with 4-PBA, an inhibitor of ER stress, significantly inhibited the expression of ER stress markers and pro-inflammatory cytokines and reduced LDH release. Furthermore, inhibiting the activity of the IRE-1α/XBP-1s pathway by STF-083010 significantly mitigated the increased levels of IL-1ß, TNF-α, and IL-6 in macrophages treated by the anti-TREM-1 antibody. XBP-1 silencing attenuated pro-inflammatory microenvironment evoked by activation of TREM-1. Besides, we found that blockade of TREM-1 with LR12 ameliorated ER stress induced by LPS in vitro and in vivo. In conclusion, we conclude that TREM-1 activation induces ER stress through the IRE-1α/XBP-1s pathway in macrophages, contributing to the pro-inflammatory microenvironment.


Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Macrófagos/patologia , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Proteína 1 de Ligação a X-Box/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Anticorpos Monoclonais/imunologia , Microambiente Celular/imunologia , Inflamação/imunologia , Interleucina-1beta/análise , Interleucina-6/análise , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/prevenção & controle , Interferência de RNA , Receptor Gatilho 1 Expresso em Células Mieloides/antagonistas & inibidores , Fator de Necrose Tumoral alfa/análise , Proteína 1 de Ligação a X-Box/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-33861712

RESUMO

The motor cortex can arouse abundant transient responses to generate complex movements with the regulation of neuromodulators, while its architecture remains unchanged. This characteristic endows humans with flexible and robust abilities in adapting to dynamic environments, which is exactly the bottleneck in the control of complex robots. In this article, inspired by the mechanisms of the motor cortex in encoding information and modulating motor commands, a biologically plausible gain-modulated recurrent neural network is proposed to control a highly redundant, coupled, and nonlinear musculoskeletal robot. As the characteristics observed in the motor cortex, this network is able to learn gain patterns for arousing transient responses to complete the desired movements, while the connections of synapses keep unchanged, and the dynamic stability of the network is maintained. A novel learning rule that mimics the mechanism of neuromodulators in regulating the learning process of the brain is put forward to learn gain patterns effectively. Meanwhile, inspired by error-based movement correction mechanism in the cerebellum, gain patterns learned from demonstration samples are leveraged as prior knowledge to improve calculation efficiency of the network in controlling novel movements. Experiments were conducted on an upper extremity musculoskeletal model with 11 muscles and a general articulated robot to perform goal-directed tasks. The results indicate that the gain-modulated neural network can effectively control a complex robot to complete various movements with high accuracy, and the proposed algorithms make it possible to realize fast generalization and incremental learning ability.

20.
Genetics ; 217(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33704438

RESUMO

Cohesin is a ring-shaped protein complex that controls dynamic chromosome structure. Cohesin activity is important for a variety of biological processes, including formation of DNA loops that regulate gene expression. The precise mechanisms by which cohesin shapes local chromosome structure and gene expression are not fully understood. Recurrent mutations in cohesin complex members have been reported in various cancers, though it is not clear whether many cohesin sequence variants have phenotypes and contribute to disease. Here, we utilized CRISPR/Cas9 genome editing to introduce a variety of cohesin sequence variants into murine embryonic stem cells and investigate their molecular and cellular consequences. Some of the cohesin variants tested caused changes to transcription, including altered expression of gene encoding lineage-specifying developmental regulators. Altered gene expression was also observed at insulated neighborhoods, where cohesin-mediated DNA loops constrain potential interactions between genes and enhancers. Furthermore, some cohesin variants altered the proliferation rate and differentiation potential of murine embryonic stem cells. This study provides a functional comparison of cohesin variants found in cancer within an isogenic system, revealing the relative roles of various cohesin perturbations on gene expression and maintenance of cellular identity.


Assuntos
Proteínas de Ciclo Celular/genética , Diferenciação Celular , Proteínas Cromossômicas não Histona/genética , Regulação Neoplásica da Expressão Gênica , Mutação , Neoplasias/genética , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Proteínas Cromossômicas não Histona/metabolismo , Elementos Facilitadores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Neoplasias/metabolismo
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