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1.
Artigo em Inglês | MEDLINE | ID: mdl-35022857

RESUMO

Metabolic pathways drive cellular behavior. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes lung tissue damage directly by targeting cells or indirectly by producing inflammatory cytokines. However, whether functional alterations are related to metabolic changes in lung cells after SARS-CoV-2 infection remains unknown. Here, we analyzed the lung single-nucleus RNA-sequencing (snRNA-seq) data of several deceased COVID-19 patients and focused on changes in transcripts associated with cellular metabolism. We observed upregulated glycolysis and oxidative phosphorylation in alveolar type 2 progenitor cells, which may block alveolar epithelial differentiation and surfactant secretion. Elevated inositol phosphate metabolism in airway progenitor cells may promote neutrophil infiltration and damage the lung barrier. Further, multiple metabolic alterations in the airway goblet cells are associated with impaired muco-ciliary clearance. Increased glycolysis, oxidative phosphorylation, and inositol phosphate metabolism not only enhance macrophage activation but also contribute to SARS-CoV-2 induced lung injury. The cytotoxicity of natural killer cells and CD8+ T cells may be enhanced by glycerolipid and inositol phosphate metabolism. Glycolytic activation in fibroblasts is related to myofibroblast differentiation and fibrogenesis. Glycolysis, oxidative phosphorylation, and glutathione metabolism may also boost the aging, apoptosis and proliferation of vascular smooth muscle cells, resulting in pulmonary arterial hypertension. In conclusion, this preliminary study revealed a possible cellular metabolic basis for the altered innate immunity, adaptive immunity, and niche cell function in the lung after SARS-CoV-2 infection. Therefore, patients with COVID-19 may benefit from therapeutic strategies targeting cellular metabolism in future.

2.
Int J Gen Med ; 15: 103-114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35023949

RESUMO

Introduction: Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, but the molecular mechanisms underlying AF are not known. We aimed to identify the pivotal genes and pathways involved in AF pathogenesis because they could become potential biomarkers and therapeutic targets of AF. Methods: The microarray datasets of GSE31821 and GSE41177 were downloaded from the Gene Expression Omnibus database. After combining the two datasets, differentially expressed genes (DEGs) were screened by the Limma package. MicroRNAs (miRNAs) confirmed experimentally to have an interaction with AF were screened through the miRTarBase database. Target genes of miRNAs were predicted using the miRNet database, and the intersection between DEGs and target genes of miRNAs, which were defined as common genes (CGs), were analyzed. Functional and pathway-enrichment analyses of DEGs and CGs were performed using the databases DAVID and KOBAS. Protein-protein interaction (PPI) network, miRNA- messenger(m) RNA network, and drug-gene network was visualized. Finally, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate the expression of hub genes in the miRNA-mRNA network. Results: Thirty-three CGs were acquired from the intersection of 65 DEGs from the integrated dataset and 9777 target genes of miRNAs. Fifteen "hub" genes were selected from the PPI network, and the miRNA-mRNA network, including 82 miRNAs and 9 target mRNAs, was constructed. Furthermore, with the validation by RT-qPCR, macrophage migration inhibitory factor (MIF), MYC proto-oncogene, bHLH transcription factor (MYC), inhibitor of differentiation 1 (ID1), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were upregulated and superoxide Dismutase 2 (SOD2) was downregulated in patients with AF compared with healthy controls. We also found MIF, MYC, and ID1 were enriched in the transforming growth factor (TGF)-ß and Hippo signaling pathway. Conclusion: We identified several pivotal genes and pathways involved in AF pathogenesis. MIF, MYC, and ID1 might participate in AF progression through the TGF-ß and Hippo signaling pathways. Our study provided new insights into the mechanisms of action of AF.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35023183

RESUMO

BACKGROUND: The PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile. AIMS: To investigate the effects of the NAFLD risk alleles on the all-cause and cause-specific mortality in 5581 Chinese adults. METHODS: The genome-wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data. RESULTS: Genome-wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 C>G variant (P = 8.6 × 10-7 ). Further analyses validated the associations of TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants with NAFLD. During 29 425.1 person-years of follow-up, the overall mortality was 816 per 100 000 person-years, where 299 deaths were attributable to cardiovascular disease and 85 to liver disease. The PNPLA3 rs738409 C>G variant was independently associated with increased liver-specific mortality (P for trend = 0.034) but reduced cardiovascular mortality (P for trend = 0.047). A composite genetic-predisposition score of PNPLA3, TM6SF2, and MBOAT7 risk alleles presented similar opposite effects on liver-specific and cardiovascular mortality. Moreover, interactions of the NAFLD risk alleles with adiposity for liver-specific mortality were found (Pinteraction  < 0.05). The reduced serum VLDL1 concentration was responsible for the increased liver-specific mortality related to NAFLD risk alleles. CONCLUSION: The PNPLA3 rs738409 C>G variant and its combination with TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants increase liver-specific mortality but reduce cardiovascular mortality in overweight/obese Chinese.

4.
Infect Agent Cancer ; 17(1): 1, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980191

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the epithelial cells of the nasopharyngeal mucosa of the head and neck. The role of long non-coding RNA and RNA methylation in NPC has received increasing attention. Therefore, this study aims to investigate the mechanism of lncRNA ZFAS1 in NPC and its relationship with RNA methylation, providing evidence for targeted therapy of NPC. METHODS: Microarray arrays were used to screen the differentially expressed miRNAs in normal tissues and tumor tissues. QRT-PCR was used to quantify ZFAS1, miR-100-3p, ATG10, autophagy and epithelial-mesenchymal transition related genes. The interactive relationship between ZFAS1 and miR-100-3p was verified using dual-luciferase reporter gene assay and RIP assay. CCK-8, transwell and apoptosis were used to detect the occurrence of tumor cells after different treatments. The m6A modification test is used to verify the effect of METTL3 on ZFAS1. BALB/c mice and BALB/c nude mice are used to detect the effects of different treatments on tumor growth and immune escape in vivo. RESULTS: ZFAS1 is upregulated in tumor tissues and NPC cells. N (6)-methyladenosine (m6A) is highly enriched in ZFAS1 and enhances its RNA stability. ZFAS1 is used as an oncogenic lncRNA, which can promote NPC cell proliferation, migration and tumor growth. In terms of mechanism, ZFAS1 up-regulates the expression of ATG10 by competitively adsorbing miR-100-3p and regulates the level of autophagy by inhibiting the PI3K/Akt signaling pathway to promote the proliferation and migration of NPC cells. CONCLUSION: In short, our study verified the cancer-promoting effect of ZFAS1 in NPC and explained part of the reason for its upregulation. In addition, we confirmed that ZFAS1 can regulate the autophagy level of NPC cells through the PI3K/AKT pathway through miR-100-3p/ATG10 to affect tumor progression.

5.
Bioengineered ; 13(1): 1235-1248, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983299

RESUMO

To date, several different types of synthetic genetic switches, including riboregulators, riboswitches, and toehold switches, have been developed to construct AND, OR, NOT, NAND, NOR, and NOT IMPLICATION (NIMP) gates. The logic gate can integrate multiple input signals following a set of algorithms and generate a response only if strictly defined conditions are met. However, there are still some logic gates that have not been implemented but are necessary to build complex genetic circuits. Here, based on the toehold switches and three-way-junction (3WJ) repressors, we designed two novel biological Boolean logic gates of IMPLICATION (IMP) and XOR. Subsequently, the outputs of these two logic gates were characterized by fluorescence analysis, indicating that they can achieve the truth tables of logical gates. Furthermore, the fluorescence intensity under the logical TRUE condition was significantly higher than under the logical FALSE condition, suggesting the high dynamic range of the ON/OFF ratios. Because of the programmability of synthetic RNA switches, the constructed RNA logic gates could serve as elementary units to build a versatile and powerful platform for translational regulation and RNA-based biological computation.

6.
Mol Med ; 28(1): 2, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983361

RESUMO

BACKGROUND: Although long noncoding RNA HLA complex group 18 (lncRNA HCG18) has been suggested to regulate cell growth in several tumours, the function of HCG18 in epithelial ovarian cancer (EOC) and its mechanism are still unclear. METHODS: shRNAs were applied to reduce HCG18 and related genes. For overexpression of miRNA, a miRNA mimic was transfected into cells. Quantitative real-time PCR (qRT-PCR) was used to detect levels of HCG18, miR-29a/b, and mRNAs. MTT, colony formation, wound healing and Transwell assays were used to evaluate cell proliferation, migration and invasion, respectively. A luciferase reporter assay was utilized to evaluate NF-κB activity and the binding of miRNAs with HCG18 or TRAF4/5. BALB nude mice injected with cells stably expressing shHCG18 or shNC were used for in vivo modelling. Subcutaneous tumour growth was monitored in nude mice, and immunohistochemistry (IHC) was used to determine expression of the proliferation marker Ki67. RESULTS: Abnormal expression of HCG18 and miR-29a/b was observed in EOC tissues. Knockdown of HCG18 using shRNA inhibited proliferation, migration, EMT and the proinflammatory pathway in EOC cells. miR-29a/b mimics and TRAF4/5 knockdown exhibited effects similar to HCG18 knockdown. Further experiments suggested that HCG18 directly targets miR-29a/b and upregulates TRAF4/5 expression, which are inhibited by targeting miR-29a/b. Moreover, overexpression of TRAF4/5 antagonized the inhibitory effect of HCG18 knockdown, suggesting that they are involved in HCG18-mediated oncogenic effects. Silencing HCG18 reduced tumour size and levels of Ki67 and TRAF4/5 while increasing miR-29a/b levels in vivo. CONCLUSIONS: Taken together, our data revealed an oncogenic signalling pathway mediated by HCG18 in ovarian cell lines, which functions as a ceRNA of miR-29a/b and thus derepresses expression levels of TRAF4/5, facilitating NF-κB pathway-mediated promotion of EOC cell proliferation and migration.

7.
J Environ Manage ; 303: 114219, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902654

RESUMO

The purpose of this study is to address the question of whether material flow cost accounting (MFCA) can contribute to the circular economy. Because MFCA is an environmental management accounting tool that simultaneously assesses company material and financial flows, it is expected to contribute to the circular economy by assisting companies to achieve both environmental and economic goals through resource efficiency. In short, the expected linkages between MFCA, company environmental and economic goals, and the circular economy are inputs, outputs, and outcomes. However, there is a lack of consensus regarding its potential, perhaps because of the scarcity of studies, with most being models and case studies without readily generalizable results. To address this gap, we analyze the triadic relationship between MFCA, environmental performance, and economic performance using a two-stage regression of data from Japanese listed companies. The main findings are as follows. Companies that implement MFCA more proactively are more likely to improve their environmental performance in terms of energy consumption, CO2 emissions, and waste produced. In turn, those that improve their environmental performance are also more likely to improve their productivity, while those that specifically improve environmental performance in terms of waste produced are also more likely to increase in profitability. Consequently, because MFCA can improve several aspects of environmental performance by saving resources, it can improve productivity by improving a range of environmental performance indicators. In particular, MFCA can improve company productivity and thereby profit, at least by reducing the amount of waste produced. This supports the view that MFCA is an effective tool to contribute to the circular economy.


Assuntos
Gerenciamento de Resíduos , Eficiência , Japão
8.
J Hazard Mater ; 424(Pt B): 127443, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34653867

RESUMO

With the increasing application of nanomaterials, evaluation of the phytotoxicity of nanoparticles has attracted considerable interest. Buckwheat is an economically pseudocereal crop, which is a potential model for investigating the response of plants to hazardous materials. In this study, the response of buckwheat to graphene oxide (GO) was investigated by integrating physiological and transcriptome analysis. GO can penetrate into buckwheat root and stem, and high concentrations of GO inhibited seedlings growth. High concentration of GO improved ROS production and regulated the activities and gene expression of oxidative enzymes, which implying GO may affect plant growth via regulating ROS detoxification. Root and stem exhibit distinct transcriptomic responses to GO, and the GO-responsive genes in stem are more enriched in cell cycle and epigenetic regulation. GO inhibited plant hormone biosynthesis and signaling by analyzing the expression data. Additionally, 97 small secreted peptides (SSPs) encoding genes were found to be involved in GO response. The gene expression of 111 transcription factor (TFs) and 43 receptor-like protein kinases (RLKs) were regulated by GO, and their expression showed high correlation with SSPs. Finally, the TFs-SSPs-RLKs signaling networks in regulating GO response were proposed. This study provides insights into the molecular responses of plants to GO.

9.
Sci Total Environ ; 806(Pt 2): 150439, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597968

RESUMO

The widespread use of antibiotics has raised global concerns, but scarce information on antibiotics in the subtropical marine environment is available. In the present study, seawater and sediment samples were collected to investigate the occurrence, spatial distribution, source, and ecological risks of 22 antibiotics in the Beibu Gulf. The total concentrations of target antibiotics (∑antibiotics) were in the range of 1.74 ng/L to 23.83 ng/L for seawater and 1.33 ng/g to 8.55 ng/g dry weight (dw) for sediment. Spatially, a decreasing trend of antibiotic levels from coast to offshore area was observed, with relatively high levels at the sites close to the Qinzhou Bay and Qiongzhou Strait. Sulfamethoxazole (SMX), trimethoprim (TMP), and norfloxacin (NOX) were predominant in seawater, while NOX, enoxacin (ENX), and enrofloxacin (ENR) were the most abundant antibiotics in sediment. In general, the sediment-water partitioning coefficients (Kd) were positively correlated with log molecular weight (MW). Salinity, particle size, and pH of water were predicted to be vital factors influencing the partition of sulfadiazine (SDZ), CIX, and ENR (p < 0.05). Livestock and aquaculture were identified as dominant sources of antibiotics in the Beibu Gulf based on PCA-MLR and Unmix model. Risk assessment revealed that SMX, CIX could pose medium risks to algae in the Beibu Gulf. Overall, our results provided paramount insights into understanding the fate and transport behaviors of antibiotics in the subtropical marine environment.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água , Antibacterianos/análise , Medição de Risco , Água , Poluentes Químicos da Água/análise
10.
Food Chem ; 371: 131125, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34563971

RESUMO

Tartary buckwheat has higher health-promoting value than common buckwheat. However, the related metabolites information except flavonoids is largely deficient. Here, we compared the seed metabolomes of the two species using a UHPLC-QqQ-MS-based metabolomics approach. In total, 722 metabolites were obtained, of which 84 and 78 were identified as the key active ingredients of Traditional Chinese Medicines and the active pharmaceutical ingredients for six major diseases-resistance, respectively. Comparative analysis showed there were obviously difference in metabolic profiles between the two buckwheat species, and further found 61 flavonoids and 94 non-flavonoids metabolites displayed significantly higher contents (≥2 fold) in Tartary buckwheat than in common buckwheat. Our results suggest that Tartary and common buckwheat seeds are rich in metabolites beneficial to human health, and non-flavonoids metabolites also contributed to Tartary buckwheat's higher health-promoting value than common buckwheat. This study provides valuable information for the development of new functional foods of Tartary buckwheat.


Assuntos
Fagopyrum , Flavonoides , Humanos , Metabolômica , Sementes
11.
J Hazard Mater ; 424(Pt A): 127296, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34592593

RESUMO

In order to produce safe rice from cadmium (Cd) contaminated soils, a special pot experiment in the field was proposed to facilitate the study of multiple remediation measures. In the field experiments, four treatments were selected for the first half of the year: rice without soil treatment (R); rice with zeolite stabilization (RZ); oilseed rape phytoremediation (OR); and inter-cropping Sedum alfredii and maize phytoremediation (IC). As the early rice with zeolite stabilization still contained elevated Cd, manganese (Mn) fertilizer was added in the late rice with a special pot experiment in the field. Results showed that, in the first crops, the grains of maize and oilseed rape contained Cd below the food standard limit, while Cd in rice grain exceeded the limit of 0.2 mg/kg. The RZ treatment did not reduce Cd in rice but decreased significantly Mn in rice straw. In the late rice, Mn fertilizer additionally reduced Cd in rice grain to 0.12 mg/kg in combination with the RZ treatment. Mn accumulation in rice straw was enhanced by Mn fertilizer. These results indicate that the pot experiment in the field provides a useful tool to further evaluate effective treatment combinations to reduce Cd in rice.


Assuntos
Oryza , Poluentes do Solo , Cádmio/análise , Cádmio/toxicidade , Manganês , Solo , Poluentes do Solo/análise
12.
Lab Anim (NY) ; 51(1): 11-21, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34916671

RESUMO

Drug delivery by lateral tail-vein injection in mice is widely used in preclinical research, but the technique is laborious to perform because the tail vein is hardly visible and too small to be cannulated. Misinjections of test components can lead to defective or even false experiment results. We present a simple but useful injection-assistant device to visualize the tail vein of mice. The device consists of a light-emitting diode (LED) circuit and a finger component. The finger component consists of an open-looped ring to slide on the finger, a slot to accommodate the mouse's tail and a lamp cage in which to set the LED lamp. Once the mouse's tail has been illuminated, the tail vein can be clearly seen as a dark line along the bright background of the tail, which facilitates venipuncture and improves the success rate of tail-vein injection. If the protocol provided has been followed correctly, a robust tail-vein injection-assistant device can be set up in 3 h with low-cost components.


Assuntos
Cauda , Animais , Injeções Intravenosas , Camundongos
13.
Enzyme Microb Technol ; 154: 109962, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34915246

RESUMO

Nanobiohybrid CAL-B/MNPs were synthesized through enzyme in situ reduction of metal ions, including noble and non-noble metals. Lipase CAL-B acted as multifunctional reagents (reducing and supporting agents). The hybrid catalysts were systematically characterized by HRTEM, EDX, MALDI-TOF-MS, and XPS analysis, confirming that highly dispersed 3-5 nm nanoparticles were evenly dispersed on lipase matrix without agglomeration. The mechanism of CAL-B reducing metal ions was investigated, revealing that AGLFFSSKDL in the amino acid sequence of CAL-B from 111 to 128 formed a stable spatial structure through hydrogen bonding, which was the key factor for enzyme in situ reduction of metal ions into highly dispersed nanoparticles.


Assuntos
Lipase , Metais , Catálise , Íons
14.
J Ethnopharmacol ; 286: 114922, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-34923087

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocyte lipid accumulation is the main feature in the early stage of nonalcoholic fatty liver disease (NAFLD). Highland barley Monascus purpureus Went (HBMPW), a fermentation product of Hordeum vulgare Linn. var. nudum Hook. f. has traditionally been used as fermented foods in Tibet with the effect of reducing blood lipid in folk medicine. AIM OF THE STUDY: This study investigated the protective effects and molecular mechanism of highland barley Monascus purpureus Went extract (HBMPWE) on NAFLD in syrian golden hamster fed with high-fat, high-fructose, high-cholesterol diet (HFFCD). MATERIALS AND METHODS: HFFCD-induced NAFLD golden hamster model was established and treated with HBMPWE. Liver index, biochemical index, and hematoxylin and eosin (HE) staining were observed. Liver metabolomics and western blot analysis were employed. RESULTS: Our study found that HBMPWE ameliorated HFFCD induced dyslipidemia, weight gain and elevated the liver index. In addition, HBMPWE treatment significantly attenuated lipid accumulation in the liver and modulated lipid metabolism (sphingolipid, glycerophospholipid). Our data demonstrated that HBMPWE not only regulated the expression of proteins related to fatty acid synthesis and decomposition (SREBP-1/ACC/FAS/AceS1, PPARα/ACSL/CPT1/ACOX1), but also regulated the expression of proteins related to cholesterol synthesis and clearance (HMGCR, LDLR, CYP7A1). CONCLUSIONS: HBMPWE improved NAFLD through multiple pathways and multiple targets in body metabolism and could be used as a functional food to treat NAFLD and other lipid metabolic disorders.

15.
Development ; 149(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34931663

RESUMO

Alveologenesis requires the coordinated modulation of the epithelial and mesenchymal compartments to generate mature alveolar saccules for efficient gas exchange. However, the molecular mechanisms underlying the epithelial-mesenchymal interaction during alveologenesis are poorly understood. Here, we report that Wnts produced by epithelial cells are crucial for neonatal alveologenesis. Deletion of the Wnt chaperone protein Wntless homolog (Wls) disrupts alveolar formation, resulting in enlarged saccules in Sftpc-Cre/Nkx2.1-Cre; Wlsloxp/loxp mutants. Although commitment of the alveolar epithelium is unaffected, α-SMA+ mesenchymal cells persist in the alveoli, accompanied by increased collagen deposition, and mutants exhibit exacerbated fibrosis following bleomycin challenge. Notably, α-SMA+ cells include a significant number of endothelial cells resembling endothelial to mesenchymal transition (EndMT), which is also present in Ager-CreER; Wlsloxp/loxp mutants following early postnatal Wls deletion. These findings provide initial evidence that epithelial-derived Wnts are crucial for the differentiation of the surrounding mesenchyme during early postnatal alveologenesis.

16.
Inorg Chem ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34854664

RESUMO

The key to developing new infrared nonlinear optical (NLO) materials is balancing second-order nonlinear optical effects and the laser-induced damage threshold (LIDT). In this paper, a new polymorph of HgBr2 (P212121) was synthesized by a "halogen-ion-induced effect" in solution, which features a crystal structure different from that of the original phase (Cmc21) and exhibits better NLO properties. Its powders show a strong SHG effect (9 × KDP), a high LIDT (30 × AgGaS2), a wide infrared transparent range, and stability in air, making it a prospective NLO material in the IR region. In addition, the above excellent NLO characteristics are well illustrated in DFT theoretical calculations. More importantly, experimental results show that the new infrared NLO polymorph with excellent comprehensive properties could be controllably obtained by using the halogen-ion-induced strategy.

17.
Mater Horiz ; 8(9): 2553-2561, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34870301

RESUMO

Biological tissues can grow stronger after damage and self-healing. However, artificial self-healing materials usually show decreased mechanical properties after repairing. Here, we develop a self-healing strengthening elastomer (SSE) by engineering kinetic stability in an ionomer. Such kinetic stability is enabled by designing large steric hindrance on the cationic groups, which prevents the structural change driven by thermodynamic instability under room temperature. However, once heat or external force is applied to disrupt the kinetic stability, the inherent thermodynamic instability induces the SSEs to form bigger and denser aggregates, thereby the material becomes stronger during the healing process. Consequently, the self-healing efficiency of fractured SSEs is as high as 143%. Unlike conventional ionomers whose mechanical properties change with time uncontrollably due to the thermodynamic instability, the SSEs show tunable self-healing strengthening behavior, thanks to the kinetic stability. This work provides a novel and universal strategy to fabricate biomimetic self-healing strengthening materials.

18.
Front Mol Biosci ; 8: 790606, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34881291

RESUMO

Protein post-translational modification by the Small Ubiquitin-like MOdifier (SUMO) on lysine residues is a reversible process highly important for transcription and protein stability. In the kidney, SUMOylation appears to be important for the cellular response to aldosterone. Therefore, in this study, we generated a SUMOylation profile of the aldosterone-sensitive kidney distal convoluted tubule (DCT) as a basis for understanding SUMOylation events in this cell type. Using mass spectrometry-based proteomics, 1037 SUMO1 and 552 SUMO2 sites, corresponding to 546 SUMO1 and 356 SUMO2 proteins, were identified from a modified mouse kidney DCT cell line (mpkDCT). SUMOylation of the renal hydrogen-coupled oligopeptide and drug co-transporter (Pept2) at one site (K139) was found to be highly regulated by aldosterone. Using immunolabelling of mouse kidney sections Pept2 was localized to DCT cells in vivo. Aldosterone stimulation of mpkDCT cell lines expressing wild-type Pept2 or mutant K139R-Pept2, post-transcriptionally increased Pept2 expression up to four-fold. Aldosterone decreased wild-type Pept2 abundance in the apical membrane domain of mpkDCT cells, but this response was absent in K139R-Pept2 expressing cells. In summary, we have generated a SUMOylation landscape of the mouse DCT and determined that SUMOylation plays an important role in the physiological regulation of Pept2 trafficking by aldosterone.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34855584

RESUMO

Text based Visual Question Answering (TextVQA) is a recently raised challenge requiring models to read text in images and answer natural language questions by jointly reasoning over the question, textual information and visual content. Introduction of this new modality - Optical Character Recognition (OCR) tokens ushers in demanding reasoning requirements. Most of the state-of-the-art (SoTA) VQA methods fail when answer these questions because of three reasons: (1) poor text reading ability; (2) lack of textual-visual reasoning capacity; and (3) choosing discriminative answering mechanism over generative couterpart (although this has been further addressed by M4C). In this paper, we propose an end-to-end structured multimodal attention (SMA) neural network to mainly solve the first two issues above. SMA first uses a structural graph representation to encode the object-object, object-text and text-text relationships appearing in the image, and then designs a multimodal graph attention network to reason over it. Finally, the outputs from the above modules are processed by a global-local attentional answering module to produce an answer splicing together tokens from both OCR and general vocabulary iteratively by following M4C.

20.
Front Public Health ; 9: 741083, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858923

RESUMO

This study aimed to investigate the association between passive smoking and physical and psychological health in Chinese nurses. Participants of this cross-sectional study comprised 2,484 non-smoking nurses. Passive smoking and demographic information were assessed using a self-administered questionnaire. Physical, psychological, and overall health status of nurses were measured using the Cornell Medical Index (CMI) health questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for nurses' health were estimated by exposure to passive smoking using unconditional logistic regression models. A total of 1,219 nurses (49.07%) were exposed to passive smoking. Of these, 609 (24.52%), 160 (6.44%), and 587 (23.63%) nurses had poorer physical, mental, and overall health, respectively. After adjusting for other confounding factors, compared with the non-passive smoking group, passive smoking was associated with poor physical (OR = 1.51, 95% CI: 1.25-1.83), mental (OR = 1.48, 95% CI: 1.07-2.07), and overall (OR = 1.58, 95% CI: 1.30-1.93) health of nurses, respectively. We also carried out subgroup analyses stratified by age, department, and professional title, which showed that most findings supported the main results. This study demonstrated that exposure to passive smoking was a risk factor for overall decreased physical and mental health status among Chinese nurses.

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