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1.
Artigo em Inglês | MEDLINE | ID: mdl-34110993

RESUMO

Face Super-Resolution (FSR) aims to infer High-Resolution (HR) face images from the captured Low-Resolution (LR) face image with the assistance of external information. Existing FSR methods are less effective for the LR face images captured with serious low-quality since the huge imaging/degradation gap caused by the different imaging scenarios (i.e., the complex practical imaging scenario that generates test LR images, the simple manual imaging degradation that generates the training LR images) is not considered in these algorithms. In this paper, we propose an image homogenization strategy via re-expression to solve this problem. In contrast to existing methods, we propose a homogenization projection in LR space and HR space as compensation for the classical LR/HR projection to formulate the FSR in a multi-stage framework. We then develop a re-expression process to bridge the gap between the complex degradation and the simple degradation, which can remove the heterogeneous factors such as serious noise and blur. To further improve the accuracy of the homogenization, we extract the image patch set that is invariant to degradation changes as Robust Neighbor Resources (RNR), with which these two homogenization projections re-express the input LR images and the initial inferred HR images successively. Both quantitative and qualitative results on the public datasets demonstrate the effectiveness of the proposed algorithm against the state-of-the-art methods.

2.
ACS Nano ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061509

RESUMO

The active color-changing ability of many living species has inspired scientists to replicate the optical property into soft wet and tissue-like hydrogel materials. However, the color-changing processes of most reported examples are controlled by the traditional stimuli (e.g., pH, temperature, and ions), which may suffer from the residual chemical product accumulation, and have difficulty in achieving local control and integration into the commercial robots, especially when applied as biomimetic skins. Herein, inspired by the nervous (bioelectricity) control of skin color change in cephalopods, we present an electrically powered multicolor fluorescent hydrogel system with asymmetric configuration that couples thermoresponsive fluorescent hydrogel with stacked graphene assembly (SGA)-based conductive paper through luminous paint as the middle layer. Owing to the highly controllable electrical stimulus in terms of amplitude and duration, the Joule heat supplied by SGA film can be regulated locally and in real time, leading to precise and local emission color control at low voltage. It also avoids the addition of any chemicals. Furthermore, the electrically powered color-changing hydrogel system can be conveniently integrated into the commercial robots as biomimetic skins that help them achieve desirable camouflage, display, or alarming functions.

3.
Front Endocrinol (Lausanne) ; 12: 656621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959100

RESUMO

Aim: The aim of this study was to assess the clinical efficacy and safety of Tripterygium-derived glycosides (TG) after 3-month and 6-month of treatments of diabetic nephropathy (DN) and to resolve the conflict between medicine guidance and clinical practice for TG application. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials involving TG application in treating DN. We extensively searched PubMed, Cochrane Library, CNKI, VIP, Wan-Fang, CBM, Chinese Clinical Trial Registry, and WHO International Clinical Trial Registration Platform till November 2020, along with grey literature for diabetes and all other relevant publications to gather eligible studies. Based on the preset inclusion and exclusion criteria, document screening, quality assessment of methodology, and data extraction was conducted by two researchers independently. The methodological quality was assessed by the Cochrane risk test from the Cochrane Handbook 5.2, and then analyses were performed by Review Manager 5.3 (Rev Man 5.3). The quality of output evidence was classified by GRADE. Results: Thirty-one eligible studies (2764 patients) were included for this meta-analysis. Our study results showed a comparable significant decrease in the 24 h-UTP and blood creatinine levels in DN patients from both 3-month and 6-month TG treatment groups, compared with the routine symptomatic treatment alone. To the contrary of the findings from the included studies, our results showed that the occurrence of serious adverse reaction events was significantly higher in the TG treated group with 6 months of treatment duration compared to that of 3 months of the treatment course. However, the total AR ratio was slightly varied while increasing the percent of severe adverse events. GRADE assessment indicated that the quality of evidence investigating TG-induced adverse reactions was moderate and that for 24 h-UTP and blood creatinine indicators were considerably low. Conclusion: Combinatorial treatment regimen including TG can significantly decrease the pathological indicators for DN progression, while it can also simultaneously predispose the patient to a higher risk for developing severe adverse events, as the medicine guidance indicates. Notably, even in 3-month of course duration smaller percent of severe adverse events can get to a fatal high percent and is likely to increase proportionally as the TG treatment continues. This suggests that TG-mediated DN treatment duration should be optimized to even less than 3 continuous months to avoid adverse event onset-associated further medical complications in DN patients. In clinical practice, serious attention should be paid to these severe side-effects even in a course normally considered safe, and importantly more high-quality studies are urgently warranted to obtain detailed insights into the balance between the efficacy and safety profiles of TG application in treating DN.

4.
Mol Med Rep ; 24(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34013363

RESUMO

Liver cancer is one of the most common types of malignant tumor, and is characterized by high malignancy, rapid progression, high morbidity and mortality. Oxaliplatin (OXA) has been reported to have marked efficiency against advanced liver cancer with tolerable toxicity. In solid tumors, the hypoxic microenvironment promotes epithelial­mesenchymal transition (EMT), which can also induce drug resistance of liver cancer to platinum drugs. Herba Cistanche (Cistanche tubulosa) has been frequently used in traditional Chinese medicine and the phenylethanol glycosides from Herba Cistanche (CPhGs) are the major active components. The present study aimed to investigate the effects of CPhGs on viability, apoptosis, migration and invasion of liver cancer cells. HepG2 liver cancer cells were divided into the control, DMSO, CoCl2, OXA, OXA + CoCl2 and CPhGs + OXA + CoCl2 groups. Subsequently, reverse transcription­quantitative PCR and western blot analysis were performed to determine the expression levels of hypoxia­inducible factor 1α (HIF­1α), lysyl oxidase­like 2 (LOXL2) and EMT­related genes and proteins (i.e., E­cadherin and Twist), in order to investigate the effects of CPhGs on liver cancer. The results demonstrated that CPhGs could enhance the effects of OXA on liver cancer, and inhibit the migration, invasion and apoptotic rate of liver cancer cells. Additionally, CPhGs treatment effectively induced downregulation of HIF­1α, LOXL2 and Twist, and upregulation of E­cadherin. The present findings indicated that CPhGs triggered a significant increase in sensitivity to OXA and suppression of hypoxia­induced EMT in liver cancer by inhibiting the HIF­1α signaling pathway. Therefore, CPhGs may be considered an effective platinum drug sensitizer, which could improve chemotherapeutic efficacy in patients with liver cancer.

5.
Adv Mater ; : e2100855, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34033149

RESUMO

With the ever-increasing adaption of large-scale energy storage systems and electric devices, the energy storage capability of batteries and supercapacitors has faced increased demand and challenges. The electrodes of these devices have experienced radical change with the introduction of nano-scale materials. As new generation materials, heterostructure materials have attracted increasing attention due to their unique interfaces, robust architectures, and synergistic effects, and thus, the ability to enhance the energy/power outputs as well as the lifespan of batteries. In this review, the recent progress in heterostructure from energy storage fields is summarized. Specifically, the fundamental natures of heterostructures, including charge redistribution, built-in electric field, and associated energy storage mechanisms, are summarized and discussed in detail. Furthermore, various synthesis routes for heterostructures in energy storage fields are roundly reviewed, and their advantages and drawbacks are analyzed. The superiorities and current achievements of heterostructure materials in lithium-ion batteries (LIBs), sodium-ion batteries (SIBs), lithium-sulfur batteries (Li-S batteries), supercapacitors, and other energy storage devices are discussed. Finally, the authors conclude with the current challenges and perspectives of the heterostructure materials for the fields of energy storage.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34029196

RESUMO

Deep learning has become the most powerful machine learning tool in the last decade. However, how to efficiently train deep neural networks remains to be thoroughly solved. The widely used minibatch stochastic gradient descent (SGD) still needs to be accelerated. As a promising tool to better understand the learning dynamic of minibatch SGD, the information bottleneck (IB) theory claims that the optimization process consists of an initial fitting phase and the following compression phase. Based on this principle, we further study typicality sampling, an efficient data selection method, and propose a new explanation of how it helps accelerate the training process of the deep networks. We show that the fitting phase depicted in the IB theory will be boosted with a high signal-to-noise ratio of gradient approximation if the typicality sampling is appropriately adopted. Furthermore, this finding also implies that the prior information of the training set is critical to the optimization process, and the better use of the most important data can help the information flow through the bottleneck faster. Both theoretical analysis and experimental results on synthetic and real-world datasets demonstrate our conclusions.

7.
Adv Mater ; : e2006494, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825222

RESUMO

Proton exchange membrane fuel cells (PEMFCs) with high efficiency and nonpollution characteristics have attracted massive attention from both academic and industrial communities due to their irreplaceable roles in building the future sustainable energy system. However, the stability issue of Pt-based catalysts for oxygen reduction reaction (ORR) has become a central constraint to the widespread deployment of the devices relative to the catalytic activity. This review aims to provide comprehensive insights into how to improve the stability of Pt-based catalysts for ORR. First, the basic physical chemistry behind the catalyst degradation, including the fundamental understandings of carbon corrosion, catalyst dissolution, and particle sintering, is highlighted. After a discussion of advanced characterization techniques for the catalyst degradation, the design strategies for improving the stability of Pt-based catalysts are summarized. Finally, further insights into the remaining challenges and future research directions are also provided.

8.
Biosens Bioelectron ; 184: 113212, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33862567

RESUMO

Methods that enable specific and sensitive detection of DNA are greatly required for high-fidelity sequence measurement and single-nucleotide variations (SNVs) genotyping. The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas systems have provided revolutionary tools for detecting nucleic acids. However, most of the current CRISPR/Cas-based DNA biosensing platforms suffer from inherent off-target effects of Cas proteins and require pre-amplification processes, which compromise the analytical fidelity. In this work, a CRISPR/Cas9-triggered hairpin probe-mediated biosensing method (namely CHP) was used to directly read the original DNA sequences, while effectively neutralizing the off-target effect and achieving high sensitivity. This technique can quantify DNA targets with a limit of detection (LOD) at the attomole level and identify SNVs with allelic fractions as low as 0.01%~0.1%. Moreover, we show that the CHP system is applicable in detecting mutations in serum samples without DNA isolation steps. Collectively, the CHP system is a sensitive and high-fidelity platform, which promises a great potential for providing robust tool for DNA sequence analysis and SNVs genotyping.


Assuntos
Técnicas Biossensoriais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , DNA/genética , Edição de Genes , Limite de Detecção
9.
J Exp Clin Cancer Res ; 40(1): 126, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33838681

RESUMO

BACKGROUND: NOD-like receptors affect multiple stages of cancer progression in many malignancies. NACHT, LRR, and PYD domain-containing protein 7 (NLRP7) is a member of the NOD-like receptor family, although its role in tumorigenesis remains unclear. By analyzing clinical samples, we found that NLRP7 protein levels were upregulated in colorectal cancer (CRC). We proposed the hypothesis that a high level of NLRP7 in CRC may promote tumor progression. Here, we further investigated the role of NLRP7 in CRC and the underlying mechanism. METHODS: NLRP7 expression in human CRC and adjacent non-tumorous tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The effect of NLRP7 in CRC progression was investigated in vitro and in vivo. Proteins interacting with NLRP7 were identified by immunoprecipitation and mass spectrometry analysis while immunofluorescence staining revealed the cellular location of the proteins. Cellular ubiquitination and protein stability assays were applied to demonstrate the ubiquitination effect on NLRP7. Cloning and mutagenesis were used to identify a lysine acceptor site that mediates NLRP7 ubiquitination. Cytokines/chemokines affected by NLRP7 were identified by RNA sequencing, qRT-PCR, and enzyme-linked immunosorbent assay. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and immunohistochemistry. RESULTS: NLRP7 protein levels, but not mRNA levels, were upregulated in CRC, and increased NLRP7 protein expression was associated with poor survival. NLRP7 promoted tumor cell proliferation and metastasis in vivo and in vitro and interacted with ubiquitin-specific protease 10, which catalyzed its deubiquitination in CRC cells. NLRP7 stability and protein levels in CRC cells were modulated by ubiquitination and deubiquitination, and NLRP7 was involved in the ubiquitin-specific protease 10 promotion of tumor progression and metastasis in CRC. K379 was an important lysine acceptor site that mediates NLRP7 ubiquitination in CRC cells. In CRC, NLRP7 promoted the polarization of pro-tumor M2-like macrophages by inducing the secretion of C-C motif chemokine ligand 2. Furthermore, NLRP7 promoted NF-κB nuclear translocation and activation of C-C motif chemokine ligand 2 transcription. CONCLUSIONS: We showed that NLRP7 promotes CRC progression and revealed an as-yet-unidentified mechanism by which NLRP7 induces the polarization of pro-tumor M2-like macrophages. These results suggest that NLRP7 could serve as a biomarker and novel therapeutic target for the treatment of CRC.

10.
BMC Anesthesiol ; 21(1): 108, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832426

RESUMO

BACKGROUND: Highly structured electroencephalography (EEG) oscillations can occur in adults during etomidate-induced general anesthesia, but the link between these two phenomena is poorly understood. Therefore, in the present study, we investigated the electroencephalogram dynamics of etomidate-induced loss of consciousness (LOC) in order to understand the neurological mechanism of etomidate-induced LOC. METHODS: This study is a prospective observational study. Etomidate-induced anesthesia was performed on eligible patients undergoing elective surgery. We analyzed EEG data from 20 patients who received etomidate for the induction of general anesthesia. We used power spectra and coherence methods to process and analyze the EEG data. Our study was based on 4-channel EEG recordings. RESULTS: Compared with the baseline (awake period), etomidate induced an increase in power in delta, theta, alpha and beta waves during LOC. Compared with the awake period, the delta-wave (1-4 Hz), alpha-wave(8-13 Hz), and theta-wave(4-8 Hz) coherence increased significantly during LOC, while the slow-wave (< 1 Hz) coherence decreased. However, the delta wave (1.0-4.0 Hz) during etomidate-induced LOC was more coherent than during the awake period (1.86-3.17 Hz, two-group test for coherence, p < 0.001). CONCLUSIONS: The neural circuit mechanism of etomidate-induced LOC is closely related to the induction of oscillation in delta, theta, alpha and beta waves and the enhancement of delta-wave coherence. TRIAL REGISTRATION: ChiCTR1800017110.

11.
J Clin Lab Anal ; 35(5): e23746, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33826163

RESUMO

BACKGROUND: Mismatch repair deficiency (dMMR) status induced by MLH1 protein deficiency plays a pivotal role in therapeutic decision-making for cancer patients. Appropriate quality control (QC) materials are necessary for monitoring the accuracy of MLH1 protein deficiency assays used in clinical laboratories. METHODS: CRISPR/Cas9 technology was used to edit the MLH1 gene of GM12878Cas9 cells to establish MLH1 protein-deficient cell lines. The positive cell lines were screened and validated by Sanger sequencing, Western blot (WB), and next-generation sequencing (NGS) and were then used to prepare formalin-fixed, paraffin-embedded (FFPE) samples through xenografting. These FFPE samples were tested by hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for suitability as novel QC materials for MLH1 protein deficiency testing. RESULTS: We successfully cultured 358 monoclonal cells, with a survival rate of 37.3% (358/960) of the sorted monoclonal cells. Through Sanger sequencing, cell lines with MLH1 gene mutation were identified. Subsequently, two cell lines with MLH1 protein deficiency were identified by WB and named as GM12878Cas9_6 and GM12878Cas9_10. The NGS results further confirmed that the MLH1 gene mutation in these two cell lines would cause the formation of stop codons and terminate the expression of the MLH1 protein. The H&E staining and IHC results also verified the deficiency of the MLH1 protein, and FFPE samples from xenografts proved their similarity and consistency with clinical samples. CONCLUSIONS: We successfully established MLH1 protein-deficient cell lines. Followed by xenografting, we developed novel FFPE QC materials with homogenous, sustainable, and typical histological structures advantages that are suitable for the standardization of clinical IHC methods.

12.
Mar Pollut Bull ; 167: 112336, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33865038

RESUMO

To improve our knowledge of the factors regulating Phaeocystis globosa colony formation, the effects of the diatom Ditylum brightwellii on P. globosa colony development were investigated using co-culture and cell-free filtrate approaches. The co-culture experiments showed the moderate abundance of D. brightwellii significantly increased the number and size of colonies, whereas a dramatically decreased effect from high abundance of D. brightwellii. The low abundance of D. brightwellii promoted early formation of P. globosa colony. The cell-free filtrate experiments indicated that culture-filtrates from the exponential phase of D. brightwellii were stimulatory for P. globosa colony formation with more and bigger colonies formed, whereas an inhibitory effect from its senescence phase filtrates. D. brightwellii may influence P. globosa colony formation by regulating the growth of P. globosa solitary cells. Our results suggest that D. brightwellii influences P. globosa colony development, but its effects vary according to its concentrations and growth phases.


Assuntos
Diatomáceas , Haptófitas , Nutrientes
13.
Signal Transduct Target Ther ; 6(1): 117, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692331

RESUMO

The Myc proto-oncogene family consists of three members, C-MYC, MYCN, and MYCL, which encodes the transcription factor c-Myc (hereafter Myc), N-Myc, and L-Myc, respectively. Myc protein orchestrates diverse physiological processes, including cell proliferation, differentiation, survival, and apoptosis. Myc modulates about 15% of the global transcriptome, and its deregulation rewires the cellular signaling modules inside tumor cells, thereby acquiring selective advantages. The deregulation of Myc occurs in >70% of human cancers, and is related to poor prognosis; hence, hyperactivated Myc oncoprotein has been proposed as an ideal drug target for decades. Nevertheless, no specific drug is currently available to directly target Myc, mainly because of its "undruggable" properties: lack of enzymatic pocket for conventional small molecules to bind; inaccessibility for antibody due to the predominant nucleus localization of Myc. Although the topic of targeting Myc has actively been reviewed in the past decades, exciting new progresses in this field keep emerging. In this review, after a comprehensive summarization of valuable sources for potential druggable targets of Myc-driven cancer, we also peer into the promising future of utilizing macropinocytosis to deliver peptides like Omomyc or antibody agents to intracellular compartment for cancer treatment.

14.
Cardiovasc Res ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757127

RESUMO

AIMS: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF. METHODS AND RESULTS: Herein, by using a fecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NLR family pyrin domain containing 3 (NLRP3)-inflammasome, promoting the development of AF which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then we conducted cross-sectional clinical studies to explore the effect of aging on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the aging phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF. CONCLUSIONS: Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease. TRANSLATIONAL PERSPECTIVE: The current study demonstrates that aged-associated microbiota dysbiosis promotes AF in part through a microbiota-gut-atria axis. Increased AF susceptibility due to enhanced atrial NLRP3-inflammasome activity by LPS and high glucose was found in an aged FMT rat model, and also confirmed within elderly clinical individuals. In a long-term FMT rat study, the AF susceptibility was ameliorated by treatment with youthful microbiota. The present findings can further increase our understanding of aged-related AF and address a promising therapeutic strategy that involves modulation of gut microbiota composition.

15.
Mol Neurodegener ; 16(1): 14, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663578

RESUMO

BACKGROUND: Before the deposition of amyloid-beta plaques and the onset of learning memory deficits, patients with Alzheimer's disease (AD) experience olfactory dysfunction, typified by a reduced ability to detect, discriminate, and identify odors. Rodent models of AD, such as the Tg2576 and APP/PS1 mice, also display impaired olfaction, accompanied by aberrant in vivo or in vitro gamma rhythms in the olfactory pathway. However, the mechanistic relationships between the electrophysiological, biochemical and behavioral phenomena remain unclear. METHODS: To address the above issues in AD models, we conducted in vivo measurement of local field potential (LFP) with a combination of in vitro electro-olfactogram (EOG), whole-cell patch and field recordings to evaluate oscillatory and synaptic function and pharmacological regulation in the olfactory pathway, particularly in the olfactory bulb (OB). Levels of protein involved in excitation and inhibition of the OB were investigated by western blotting and fluorescence staining, while behavioral studies assessed olfaction and memory function. RESULTS: LFP measurements demonstrated an increase in gamma oscillations in the OB accompanied by altered olfactory behavior in both APP/PS1 and 3xTg mice at 3-5 months old, i.e. an age before the onset of plaque formation. Fewer olfactory sensory neurons (OSNs) and a reduced EOG contributed to a decrease in the excitatory responses of M/T cells, suggesting a decreased ability of M/T cells to trigger interneuron GABA release indicated by altered paired-pulse ratio (PPR), a presynaptic parameter. Postsynaptically, there was a compensatory increase in levels of GABAAR α1 and ß3 subunits and subsequent higher amplitude of inhibitory responses. Strikingly, the GABA uptake inhibitor tiagabine (TGB) ameliorated abnormal gamma oscillations and levels of GABAAR subunits, suggesting a potential therapeutic strategy for early AD symptoms. These findings reveal increased gamma oscillations in the OB as a core indicator prior to onset of AD and uncover mechanisms underlying aberrant gamma activity in the OB. CONCLUSIONS: This study suggests that the concomitant dysfunction of both olfactory behavior and gamma oscillations have important implications for early AD diagnosis: in particular, awareness of aberrant GABAergic signaling mechanisms might both aid diagnosis and suggest therapeutic strategies for olfactory damage in AD.

16.
Front Med ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33660217

RESUMO

Synthetic lethal screening, which exploits the combination of mutations that result in cell death, is a promising method for identifying novel drug targets. This method provides a new avenue for targeting "undruggable" proteins, such as c-Myc. Here, we revisit current methods used to target c-Myc and discuss the important functional nodes related to c-Myc in non-oncogene addicted network, whose inhibition may cause a catastrophe for tumor cell destiny but not for normal cells. We further discuss strategies to identify these functional nodes in the context of synthetic lethality. We review the progress and shortcomings of this research field and look forward to opportunities offered by synthetic lethal screening to treat tumors potently.

17.
Neurol Res ; 43(5): 358-371, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33749522

RESUMO

OBJECTIVES: Aberrant microglial responses promote neuroinflammation in neurodegenerative diseases. However, rifampicin's effect on cognitive and motor sequelae of inflammation remains unknown. Therefore, we investigated whether rifampicin exerts neuroprotection against lipopolysaccharide (LPS)-induced cognitive and motor impairments. METHODS: A mouse model of LPS-induced cognitive and motor impairment was established. Adult C57BL/6 mice were injected intraperitoneally with 25 mg/kg rifampicin 30 min before intraperitoneal microinjection of LPS (750 µg/kg) daily until study end. Treatments and behavioral experiments were performed once daily for 7 days. Behavioral tests and pathological/biochemical assays were performed to evaluate LPS-induced damage to the hippocampus and substantia nigra (SN). RESULTS: Rifampicin attenuated LPS-induced cognitive and motor impairments, based on performance in the behavioral tests. Rifampicin suppressed the release of pro-inflammatory mediators, including tumor necrosis factor-α, interleukin-1ß, and prostaglandin E2 in the serum and nitric oxide (NO) in brain tissue, and cyclooxygenase-2 and inducible nitric oxide synthase levels. Immunofluorescence revealed that rifampicin inhibited LPS-induced microglial activation in the hippocampus and SN, thus protecting the neurons. Rifampicin inhibited the activation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. Rifampicin downregulated TLR4 and MyD88 protein levels and inhibited NF-κB inhibitor alpha and NF-κB inhibitor kinase beta phosphorylation, thus reducing p65 nuclear transfer by inhibiting NF-κB signaling activation in LPS-treated mice. CONCLUSION: Rifampicin protects against LPS-induced neuroinflammation and attenuates cognitive and motor impairments by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Our findings might aid the development of novel therapies to treat progressive neurodegenerative diseases.

18.
Ecotoxicology ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544316

RESUMO

Evidence from terrestrial sedimentary heavy metals record is a robust indicator of anthropogenic activity changes. Heavy metals and particle sizes in 210Pb-dated sediment cores extracted from Hulun and Chagan lakes were measured to reconstruct the sediment record and evaluated health risk of heavy metals in the last 150 years in Northeast China. In general, the particle size of Hulun Lake was finer with more contents of clay than Chagan Lake, while the concentrations of most heavy metals in Hulun Lake was lower. Prior to the 1970s, significant positive correlations between most heavy metals and clay, indicating that that they were likely co-transported and both lakes were dominated by natural inputs. The two records showed significant increases in concentrations of heavy metals between 1970s and 1990s, which were associated with recent anthropogenic activities derived from principal component analysis of clay and heavy metals. Specifically, the exploitation of mineral resources and traffic source in the Hulun Lake, and the emissions of pesticides and fertilizers from agricultural activity, and the combustions of coal and fossil fuels from industrial activity in the Chagan Lake. Since 1990s, natural processes was the main source of heavy metals in Hulun Lake due to the environmental protection policy, while emissions of industrial, agricultural and domestic sewage were still the main source in Chagan Lake. Overall carcinogenic risks caused by single heavy metal elements determined for the two lakes were considered to be acceptable. However, Cr was associated with a risk for children across since 1970s which should be paid more attention.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33621038

RESUMO

The success of n-type doping has attracted strong research interest for exploring effective n-type dopants for Mg3Sb2 thermoelectrics. Herein, we experimentally study Gd and Ho as n-type dopants for Mg3Sb2 thermoelectrics. The synthesis, structural characterization, and thermoelectric properties of Gd-doped, Ho-doped, (Gd, Te)-codoped, and (Ho, Te)-codoped Mg3Sb2 samples are reported. It is found that Gd and Ho are effective n-type cation-site dopants showing a higher doping efficiency as well as a superior carrier concentration in comparison with anion-site doping with Te, consistent with the previous theoretical prediction. For n-type Mg3Sb2 samples doped with Gd or Ho, optimal thermoelectric figure of merit zT values of ∼1.26 and ∼0.94 at 725 K are obtained, respectively, in Mg3.5Gd0.04Sb2 and Mg3.5Ho0.04Sb2, which are superior to many reported Te-doped Mg3Sb2 without alloying with Mg3Bi2. By codoping with Gd (or Ho) and Te, reduced thermal conductivity and enhanced power factor values are achieved at high temperatures, which results in enhanced peak zT values well above unity at 725 K. This work reveals Gd and Ho as effective n-type dopants for Mg3Sb2 thermoelectric materials.

20.
Plant Physiol Biochem ; 160: 352-364, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33548802

RESUMO

In Fraxinus mandshurica, we successfully isolated and identified the loose, uniform and creamy-white cambial meristematic cells (CMCs) from newborn shoots, and established a culture technology for induction, proliferation and differentiation of CMCs. In this technology, higher induction rate (83.0%, 0.57-fold to the control) was obtained by an effective pretreatment after 28-day induction culture, CMCs can be better proliferation cultured than common calli and maintain same growth states after several times of cultures and 3.3% CMCs primarily realized differentiation. Gene expressions in the differentiated CMCs revealed that, low expression of FmWOX5 (regulator in establishment of competence for shoot formation, 0.09-fold to the control) and high expressions of FmWOX4 (cambium stem cell regulator, 16.7-fold to the control) and 9 key genes in shoot regeneration (2.4-fold-72.1-fold to the control) function in CMCs differentiation. In addition to the function of high expression of PHAVOLUTA (FmPHV) in CMCs differentiation (5.4-fold-157.3-fold to undifferentiated CMCs), functions of high expression of FmPHV in CMCs identification (22.4-fold to common calli) and generating more shoots (2.3-fold to the control) by significantly changing expressions of key regulators in HD-Zip Class III related shoot regeneration networks in positive transgenic plants through the hypocotyl transforming system in F. mandshurica, were further revealed. These works were of profound significance in providing the culture technology of CMCs from newborn shoots in F. mandshurica for the first time and revealing the positive functions of FmPHV in CMCs identification and differentiation in F. mandshurica and promoting the shoot regeneration by hypocotyls.


Assuntos
Câmbio/citologia , Fraxinus/crescimento & desenvolvimento , Hipocótilo/crescimento & desenvolvimento , Brotos de Planta/citologia , Técnicas de Cultura de Tecidos , Diferenciação Celular , Fraxinus/citologia , Hipocótilo/citologia
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