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1.
J Hazard Mater ; 423(Pt B): 127159, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34537633

RESUMO

Melatonin, a regulatory molecule, performs pleiotropic functions in plants, including aluminum (Al) stress mitigation. Here, we conducted transcriptomic and physiological analyses to identify metabolic processes associated with the alleviated Al-induced growth inhibition of the melatonin-treated (MT) maize (Zea mays L.) seedlings. Melatonin decreased Al concentration in maize roots and leaves under Al stress. Al stress reduced the total dry weight (DW) by 41.2% after 7 days of treatment. By contrast, the total DW was decreased by only 19.4% in MT plants. According to RNA-Seq, enzyme activity, and metabolite content data, MT plants exhibited a higher level of relatively stable carbon and nitrogen metabolism than non-treated (NT) plants. Under Al stress, MT plants showed higher photosynthetic rate and sucrose content by 29.9% and 20.5% than NT plants, respectively. Similarly, the nitrate reductase activity and protein content of MT plants were 34.0% and 15.0% higher than those of NT plants, respectively. Furthermore, exogenous supply of melatonin mitigated Al-induced oxidative stress. Overall, our results suggest that melatonin alleviates aluminum-induced growth inhibition through modulating carbon and nitrogen metabolism, and reestablishing redox homeostasis in maize. Graphical Abstarct.

2.
Fitoterapia ; : 105091, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34826555

RESUMO

Ten undescribed cadinane-type sesquiterpenes (1-10) were isolated from the whole plant of Eupatorium chinense. Their planar structures were mainly elucidated by extensive analysis of spectroscopic data and DFT NMR calculations. The absolute configurations of 1, 2, and 3 were determined by TDDFT ECD calculations while those of compounds 4-7 and 9 were confirmed by single crystal X-ray diffraction experiments. Compounds 2 and 3 are a pair of C-10 epimers, compounds 4 and 5 a pair of C-1 epimers, and compounds 9 and 10 a pair of compounds isomerized at both C-1 and C-10. A possible biosynthetic pathway for these new sesquiterpenes was proposed.

3.
Bioresour Technol ; : 126407, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34826564

RESUMO

Syngas from pyrolysis/gasification process is a mixture of CO, CO2 and H2, which could be bio-converted to CH4, so called syngas biomethanation. Its development is obstructed due to the low productivity and CO inhibition. The aim of this study was to demonstrate the feasibility of using syngas as the only carbon source containing high CO concentration (40%) for biomethanation. Lab-scale thermophilic bioreactor inoculated with anaerobic sludge was operated continuously for over 900 hours and the shift of microbial structure were investigated. Results showed that thermophilic condition was suitable for syngas biomethanation and the microbes could adapt to high CO concentration. Higher processing capacity of 12.6 m3/m3/d was found and volumetric methane yield of 2.97 m3/m3/d was observed. These findings could strengthen the theoretical basis of syngas biomethanation and support its industrialization in the future.

4.
Cell Mol Immunol ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785732

RESUMO

The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis (IAC). How this axis is regulated to modulate IAC remains unknown. Here, we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6, as well as another IL-6 subfamily member, Oncostatin M (OSM). MARCH3 is associated with the IL-6 receptor α-chain (IL-6Rα) and its coreceptor gp130. Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rα at K401 and gp130 at K849 following IL-6 stimulation, leading to their translocation to and degradation in lysosomes. MARCH3 deficiency increases IL-6- and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types. MARCH3 deficiency enhances dextran sulfate sodium (DSS)-induced STAT3 activation, increases the expression of inflammatory cytokines, and exacerbates colitis, as well as azoxymethane (AOM)/DSS-induced colitis-associated cancer in mice. In addition, MARCH3 is downregulated in human colorectal cancer tissues and associated with poor survival across different cancer types. Our findings suggest that MARCH3 is a pivotal negative regulator of IL-6-induced STAT3 activation, inflammation, and inflammation-associated carcinogenesis.

5.
Opt Express ; 29(24): 40397-40405, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809381

RESUMO

In this paper, we investigated the impact of the linewidth of a QCW pulsed sodium laser on the brightness performance of a generating sodium laser guide star by using the numerical simulation tool PRS. We compared the field test results with the simulation results for two TIPC's 30W class sodium guide star lasers and found the results are in good agreement which proves the tool can be used for prediction. Then, we used the tool to study the influence of D2b repumping and different linewidths from 10MHz to 1GHz on the coupling efficiency and the photon return flux. For the TIPC's QCW pulsed solid-state laser, when the on-sky power density is 1 W/m2, the coupling efficiency is 79.6 (photons/s/W/(atoms/m2)) without D2b repumping, however, the value is up to 213.3 (photons/s/W/(atoms/m2)) with 15% D2b enabled and is increased by 168% than the value without D2b; when the power density reaches 10 W/m2, the coupling efficiencies without D2b and with 15% D2b are 66.6 and 233.6 (photons/s/W/(atoms/m2)), respectively. The results show that for the QCW pulsed laser, D2b repumping is necessary. With D2b enabled, if the spectral linewidth is too wide or too narrow, the photon return flux will be adversely affected. The return flux of 60MHz is 52.5% higher than that of 1GHz, while the return flux of 300MHz is 37.8% higher than that of 10 MHz when the laser power is 100W.

6.
J Med Chem ; 64(22): 16328-16348, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34735773

RESUMO

Activated Cdc42-associated kinase 1 (ACK1/TNK2) is a nonreceptor tyrosine kinase with a unique structure. It not only can act as an activated transmembrane effector of receptor tyrosine kinases (RTKs) to transmit various RTK signals but also can play a corresponding role in epigenetic regulation. A number of studies have shown that ACK1 is a carcinogenic factor. Blockage of ACK1 has been proven to be able to inhibit cancer cell survival, proliferation, migration, and radiation resistance. Thus, ACK1 is a promising potential antitumor target. To date, despite many efforts to develop ACK1 inhibitors, no specific small molecule inhibitors have entered clinical trials. This Perspective provides an overview of the structural features, biological functions, and association with diseases of ACK1 and in vitro and in vivo activities, selectivity, and therapeutic potential of small molecule ACK1 inhibitors with different chemotypes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34806139

RESUMO

Keratinase is one of the important proteases, which is widely used for converting keratin of the keratinaceous materials into various value-added products. In this study, a popular keratinase producer, Bacillus licheniformis PWD-1, was exposed to ultraviolet (UV) and He-Ne laser irradiations to develop high keratinase-producing mutants. Laser irradiation showed a higher lethality of cells (94%) than UV treatment (92%), whereas laser treatment required a longer time (75 min) than UV treatment (20 min). A total of 58 mutants were selected from 176 isolates to study protein and keratinase production capability of the mutants. The highest keratin-to-casein (K:C) ratio (1.43) was exhibited by LU11 mutant, which was obtained from the combined laser and UV irradiations. The purified keratinase (65 kDa) of LU11 showed 40% yield 1.7-fold purity, while the respective value for wild enzyme was 29% and 1.3-fold. Both enzymes showed optimal activity at 55 ℃ and pH 8, with a Z value of 15.78 ℃ for LU11 and 19.72 ℃ for wild strain. The Vmax and specific constant (Kcat/Km) of the mutant enzyme were 357.17 U/ml and 33.11 min-1 mM-1, respectively, which were significantly higher than the respective values of wild enzyme (102.04 U/ml and 28.36 min-1 mM-1).

8.
Bioresour Technol ; : 126353, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34798256

RESUMO

This study evaluated the effects of bio-based carbon materials on methane production by anaerobic digestion. The results showed that biochar and hydrochar can promote cumulative methane yield by 15% to 29%. However, there was no statistical significance (p>0.05) between hydrochar and biochar produced at different temperature on methane production. 16S rRNA gene sequencing and bioinformatics analysis showed that biochar and hydrochar enriched microorganism that might participate in direct interspecies electron transfer (DIET) such as Pseudomonadaceae, Bacillaceae, and Clostridiaceae. The the surface properties of the modified biochar were characterized with BET, Raman, FTIR and XPS. Bio-based carbon materials with uniform dispersion provided a stable environment for the DIET of microorganisms and electrons are transferred through aromatic functional groups on the surface of materials. This study reveals bio-based carbon materials surface properties on methane production in anaerobic digestion and provides a new approach to recycling spent coffee grounds.

9.
Acta Pharm Sin B ; 11(10): 3092-3104, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34729303

RESUMO

Mitotic catastrophe (MC) is a form of programmed cell death induced by mitotic process disorders, which is very important in tumor prevention, development, and drug resistance. Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study, it is urgent for us to develop a professional and comprehensive database to curate MC-related data. Mitotic Catastrophe Database (MCDB) consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles. Also, MCDB defines the confidence level, classification criteria, and uniform naming rules for MC-related data, which greatly improves data reliability and retrieval convenience. Moreover, MCDB develops protein sequence alignment and target prediction functions. The former can be used to predict new potential MC-related genes and proteins, and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds. In short, MCDB is such a proprietary, standard, and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry, molecular biology, bioinformatics, oncology and so on. The MCDB is distributed on http://www.combio-lezhang.online/MCDB/index_html/.

10.
Acta Pharm Sin B ; 11(10): 3015-3034, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34729301

RESUMO

Parkinson's disease (PD), known as one of the most universal neurodegenerative diseases, is a serious threat to the health of the elderly. The current treatment has been demonstrated to relieve symptoms, and the discovery of new small-molecule compounds has been regarded as a promising strategy. Of note, the homeostasis of the autolysosome pathway (ALP) is closely associated with PD, and impaired autophagy may cause the death of neurons and thereby accelerating the progress of PD. Thus, pharmacological targeting autophagy with small-molecule compounds has been drawn a rising attention so far. In this review, we focus on summarizing several autophagy-associated targets, such as AMPK, mTORC1, ULK1, IMPase, LRRK2, beclin-1, TFEB, GCase, ERRα, C-Abelson, and as well as their relevant small-molecule compounds in PD models, which will shed light on a clue on exploiting more potential targeted small-molecule drugs tracking PD treatment in the near future.

12.
Scand J Gastroenterol ; : 1-6, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592854

RESUMO

BACKGROUND: Over the past decades, the incidence and prevalence of pancreatic neuroendocrine neoplasms (pNENs) have steadily increased. However, accurate prediction of the prognosis and treatment of this condition are currently challenging. This study aims to develop and validate a personalized nomogram to predict the survival of patients with pNENs. MATERIALS AND METHODS: A total of 9739 patients with pNENs were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. Subsequently, the patients were randomly assigned to a derivation cohort (n = 6874) and a validation cohort (n = 2865). The survival of patients was assessed using the Cox proportional hazards (PHs) regression analysis. Then, the nomogram that predicted 3-and 5-year survival rates were developed in the derivation cohort. Further, the predictive performance of the nomogram was evaluated through discrimination and calibration. RESULTS: The Cox regression analysis revealed that age, differentiation, the extent of tumor, M staging, and surgery were independent prognostic predictors for pNENs. The nomogram showed superior discrimination capability than AJCC staging in both derived and validation cohorts (C-index: 0.874 versus 0.721 and 0.833 versus 0.721). The calibration curves showed that the practical and predicted survival rates effectively coincided, specifically for the 3-year survival rate. CONCLUSION: Our nomogram is a valuable tool for the prediction of the survival rate for patients with pNENs; this may promote individualized prognostic evaluation and treatment.

15.
Med Res Rev ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633088

RESUMO

Bromodomain-containing protein 4 (BRD4), as the most studied member of the bromodomain and extra-terminal (BET) family, is a chromatin reader protein interpreting epigenetic codes through binding to acetylated histones and non-histone proteins, thereby regulating diverse cellular processes including cell cycle, cell differentiation, and cell proliferation. As a promising drug target, BRD4 function is closely related to cancer, inflammation, cardiovascular disease, and liver fibrosis. Currently, clinical resistance to BET inhibitors has limited their applications but synergistic antitumor effects have been observed when used in combination with other tumor inhibitors targeting additional cellular components such as PLK1, HDAC, CDK, and PARP1. Therefore, designing dual-target inhibitors of BET bromodomains is a rational strategy in cancer treatment to increase potency and reduce drug resistance. This review summarizes the protein structures and biological functions of BRD4 and discusses recent advances of dual BET inhibitors from a medicinal chemistry perspective. We also discuss the current design and discovery strategies for dual BET inhibitors, providing insight into potential discovery of additional dual-target BET inhibitors.

17.
J Agric Food Chem ; 69(39): 11626-11636, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34554747

RESUMO

Crocetin, a high-value apocarotenoid in saffron, is widely applied to the fields of food and medicine. However, the existing method of obtaining crocetin through large-scale cultivation is far from meeting the market demand. Microbial synthesis of crocetin is a potential alternative to traditional resources, and it is found that carotenoid cleavage dioxygenase (CCD) is the critical enzyme to synthesize crocetin. So, in this study, we used "hybrid-tunnel" engineering to obtain variants of Crocus sativus-derived CsCCD2, essential for zeaxanthin conversion into crocetin, with a broader substrate specificity and higher catalytic efficiency. Variants including S323A, with a lower charge bias and a larger tunnel size than the wild-type, showed a 5-fold higher crocetin titer in yeast-based fermentations. S323A could also convert the ß-carotene substrate to crocetin dialdehyde and exhibited a 12.83-fold greater catalytic efficiency (kcat/Km) toward zeaxanthin than the wild-type in vitro. This strategy enabled the production of 107 mg/L crocetin in 5 L fed-batch fermentation, higher than that previously reported. Our findings demonstrate that engineering access tunnels to expand the substrate profile by in silico protein design represents a viable strategy to refine the catalytic properties of enzymes across a range of applications.


Assuntos
Crocus , Dioxigenases , Carotenoides , Vitamina A/análogos & derivados , Zeaxantinas
19.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576166

RESUMO

Salmonella enterica serovar Typhi (S. Typhi) is a human-limited intracellular pathogen and the cause of typhoid fever, a severe systemic disease. Pathogen-host interaction at the metabolic level affects the pathogenicity of intracellular pathogens, but it remains unclear how S. Typhi infection influences host metabolism for its own benefit. Herein, using metabolomics and transcriptomics analyses, combined with in vitro and in vivo infection assays, we investigated metabolic responses in human macrophages during S. Typhi infection, and the impact of these responses on S. Typhi intracellular replication and systemic pathogenicity. We observed increased glucose content, higher rates of glucose uptake and glycolysis, and decreased oxidative phosphorylation in S. Typhi-infected human primary macrophages. Replication in human macrophages and the bacterial burden in systemic organs of humanized mice were reduced by either the inhibition of host glucose uptake or a mutation of the bacterial glucose uptake system, indicating that S. Typhi utilizes host-derived glucose to enhance intracellular replication and virulence. Thus, S. Typhi promotes its pathogenicity by inducing metabolic changes in host macrophages and utilizing the glucose that subsequently accumulates as a nutrient for intracellular replication. Our findings provide the first metabolic signature of S. Typhi-infected host cells and identifies a new strategy utilized by S. Typhi for intracellular replication.


Assuntos
Glucose/metabolismo , Salmonella typhi/patogenicidade , Febre Tifoide/metabolismo , Febre Tifoide/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Macrófagos/metabolismo , Macrófagos/microbiologia , Virulência
20.
Front Endocrinol (Lausanne) ; 12: 716082, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335480

RESUMO

Objective: To analyze the incidence and risk factors for lateral lymph node metastases (LNMs) in T1a papillary thyroid carcinoma (PTC) with a focus on tumor location and size. Materials and Methods: The incidence of lateral LNM in 345 cases of T1a PTC was retrospectively analyzed. Univariate and multivariate analyses were performed to assess the relationships between lateral LNM and clinicopathological characteristics. Results: The incidence of skip metastasis to lateral LNM in T1a PTC located in the upper lobe was 12.1% (8/66). Logistic regression analysis indicated tumor size >5 mm (OR = 5.04, 95% CI = 1.79 to 14.18, P = 0.002), upper lobe location (OR = 7.68, 95% CI = 3.05-19.34, P < 0.001) and the number of central neck LNM (<2: OR = 24.79, 95% CI = 8.23-74.60, P < 0.001; ≥2: OR = 4.99, 95% CI = 1.95-12.73, P < 0.001) were independently associated with lateral LNM. Comparing the lateral and central LNM stratification based on tumor location revealed that both the incidences of lateral (33.3%) and central (30.3%) LNM of T1a PTC located in the upper lobe were higher than those of T1a PTC located in the middle and lower lobes. Of T1a PTC located in the upper lobe, the incidence of lateral LNM was 33.3% (22/66), which was higher than that [30.3% (20/66)] of central LNM. This finding is reversed in all T1a PTC cases and T1a PTC cases with tumor located in the middle and lower lobes. Conclusion: A particularly high likelihood of lateral LNM was observed in T1a PTC patients with tumor located in the upper lobe of the thyroid gland, especially the tumor >5 mm in size, which could be considered a risk factor for lateral LNM in the clinical management of T1a PTC.

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