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1.
Food Chem ; 366: 130583, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34303203

RESUMO

Terpenoid metabolism at different developmental stages of Carya cathayensis was elucidated based on LC-MS/MS analysis and multi-omics. Terpenoid metabolites 2-hydroxy-1,4-naphoquinone and 3-hydroxybenzoic acid reached the maximum at 105 days after pollination (DAP) (P2 stage). To reveal the complex mechanism of C. cathayensis embryogenesis in relation to terpenoid metabolites (90-165 DAP), a metabolomic and transcriptional co-expression analysis was conducted. Based on RNA-Seq analysis, 679 genes of 1144 terpenoid biosynthesis were differentially expressed. Six terpenoid metabolites and 86 differentially expressed genes related to terpenoquinone metabolism were identified. Comprehensive analysis of metabolome and transcriptional data revealed that terpenoquinone accumulated in the early phase was active in the later phase. Overall, we profiled the transcriptome and metabolome changes in C. cathayensis during the developmental phase to investigate the metabolic pathways and candidate genes underlying the changes at different growth stages.


Assuntos
Carya , Cromatografia Líquida , Perfilação da Expressão Gênica , Espectrometria de Massas em Tandem , Terpenos , Transcriptoma
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1623-1630, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627451

RESUMO

OBJECTIVE: To investigate the effect of lysosomal-associated protein transmembrane-4 Beta(Laptm4b) deletion on hematopoietic stem/progenitor cells (HSPCs) homeostasis in mice. METHODS: The hematopoietic system specific Laptm4b-deficient mice were constructed. The number and proportion of HSPCs (LSK, LT, ST, MPP, etc) in Laptm4b-deficient mice were analyzed by flow cytometry. Single SLAM-HSC cell was sorted by flow sorter and cultured in vitro to measure the effect of Laptm4b deletion on the colony forming ability of hematopoietic stem cells (HSCs). The effect of Laptm4b-deficient on the reconstitution ability of HSCs in mice was detected by competitive transplantation experiment of SLAM-HSC cells. RESULTS: Laptm4b deficiency could moderately upregulate the proportion of T cells in the peripheral blood of the mice, but showed no significant effect on the proportion and number of HSPCs. Laptm4b deletion showed no effect on the reconstruction ability of HSCs after competitive transplantation, but it could inhibit the colony formation of HSCs in vitro. CONCLUSION: LAPTM4B may play a role in HSCs under the proliferation stress. Laptm4b-deficient in mice hematopoietic system showed no significant effect on the HSPCs homeostasis maintenance and reconstruction ability.


Assuntos
Células-Tronco Hematopoéticas , Fatores de Transcrição , Animais , Proliferação de Células , Citometria de Fluxo , Homeostase , Camundongos
3.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34638687

RESUMO

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system-related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate the antiviral effect on the exosomes of teleost fish. Exosomes isolated from mandarin fish serum by ultra-centrifugation were internalized by mandarin fish fry cells and were able to inhibit Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigate the underlying mechanisms of exosomes in inhibiting ISKNV infection, the protein composition of serum-derived exosomes was analyzed by mass spectrometry. It was found that myxovirus resistance 1 (Mx1) was incorporated by exosomes. Furthermore, the mandarin fish Mx1 protein was proven to be transferred into the recipient cells though exosomes. Our results showed that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication, which suggested an underlying mechanism of the exosome antivirus in that it incorporates Mx1 protein and delivery into recipient cells. This study provided evidence for the important antiviral role of exosomes in the immune system of teleost fish.

4.
Colloids Surf B Biointerfaces ; 208: 112140, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34597939

RESUMO

Semiconductor quantum dots (QDs) have been extensively explored for extensive bioapplications, yet their cellular fate, especially exocytosis, has not been thoroughly investigated. Herein, we systematically investigated the whole cellular process from the endocytosis, intercellular trafficking, to the exocytosis of a typical QD, core/shell CdSe/ZnS QD. Using confocal laser scanning microscopy and flow cytometry, and after carefully eliminating the effect of cell division, we found that the QDs were internalized by HeLa cells with a time-, dose-, and serum-dependent manner. The cellular uptake was inhibited by serum, but eventually peaked after 4-6 h incubation with or without serum. The primary endocytosis pathway was clathrin-mediated, and actin- and microtubule-dependent in the medium with serum, while the caveolae-mediated endocytosis and macropinocytosis were more important for the QDs in the serum-free medium. Inside cells, most QDs distributed in lysosomes, and some entered mitochondria, endoplasmic reticulum, and Golgi apparatus. The translocation of the QDs from other organelles to Golgi apparatus was observed. The exocytosis of QDs was faster than the endocytosis, reaching the maximum in about one hour after cultured in fresh culture medium, with around 60% of the internalized QDs remained undischarged. The exocytosis process was energy- and actin-dependent, and the lysosome exocytosis and endoplasmic reticulum/Golgi pathway were the main routes. This study provides a full picture of behavior and fate of QDs in cells, which may facilitate the design of ideal QDs applied in biomedical and other fields.

5.
Pharmacol Ther ; : 108004, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34597754

RESUMO

The liver has the ability to repair itself after injury; however, a variety of pathological changes in the liver can affect its ability to regenerate, and this could lead to liver failure. Mesenchymal stem cells (MSCs) are considered a good source of cells for regenerative medicine, as they regulate liver regeneration through different mechanisms, and their efficacy has been demonstrated by many animal experiments and clinical studies. Induced pluripotent stem cells, another good source of MSCs, have also made great progress in the establishment of organoids, such as liver disease models, and in drug screening. Owing to the recent developments in MSCs and induced pluripotent stem cells, combined with emerging technologies including graphene, nano-biomaterials, and gene editing, precision medicine and individualized clinical treatment may be realized in the near future.

6.
Cell Death Dis ; 12(10): 918, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620839

RESUMO

Pancreatic cancer is the third leading cause of cancer-related mortalities and is characterized by rapid disease progression. Identification of novel therapeutic targets for this devastating disease is important. Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme of gluconeogenesis. The current study tested the expression and potential functions of PCK1 in pancreatic cancer. We show that PCK1 mRNA and protein levels are significantly elevated in human pancreatic cancer tissues and cells. In established and primary pancreatic cancer cells, PCK1 silencing (by shRNA) or CRISPR/Cas9-induced PCK1 knockout potently inhibited cell growth, proliferation, migration and invasion, and induced robust apoptosis activation. Conversely, ectopic overexpression of PCK1 in pancreatic cancer cells accelerated cell proliferation and migration. RNA-seq analyzing of differentially expressed genes (DEGs) in PCK1-silenced pancreatic cancer cells implied that DEGs were enriched in the PI3K-Akt-mTOR cascade. In pancreatic cancer cells, Akt-mTOR activation was largely inhibited by PCK1 shRNA, but was augmented after ectopic PCK1 overexpression. In vivo, the growth of PCK1 shRNA-bearing PANC-1 xenografts was largely inhibited in nude mice. Akt-mTOR activation was suppressed in PCK1 shRNA-expressing PANC-1 xenograft tissues. Collectively, PCK1 is a potential therapeutic target for pancreatic cancer.

7.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1867(1): 159061, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34610469

RESUMO

Trans fatty acids (TFA) in food can cause liver inflammation. Activation of NOD-like receptor protein-3 (NLRP3) inflammasome is a key factor in the regulation of inflammation. Accumulating evidence suggests that ERS-induced NLRP3 inflammasome activation underlies the pathological basis of various inflammatory diseases, but the precise mechanism has not been fully elucidated. Therefore, this paper focused on TFA, represented by elaidic acid (EA), to investigate the mechanism of liver inflammation. Levels of mRNA and protein were detected by RT-qPCR and Western blotting, the release of proinflammatory cytokines was measured by ELISA, and intracellular Ca2+ levels were determined by flow cytometer using Fluo 4-AM fluorescent probes. Our research indicated that EA induced the endoplasmic reticulum stress (ERS) response in Kupffer cells (KCs), accompanied by the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which resulted in NLRP3 inflammasome formation, and eventually increased the release of inflammatory factors. NLRP3 inflammasome activation was inhibited when KCs were pretreated with ERS inhibitors (4-PBA) and MAPK selective inhibitors. Furthermore, when ERS was blocked, the MAPK pathway was inhibited.

8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 832-838, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622601

RESUMO

Objective: To study the distributional characteristics of allergens in children with allergic diseases in Shaanxi province. Methods: A total of 4 622 children diagnosed with allergic diseases in the Asthma Center, Department of Pediatrics, Xijing Hospital from March 2015 to February 2019 were selected. Serum allergen-specific immunoglobulin E (sIgE) of 19 common kinds of allergens were examined with enzyme-linked immunosorbent assay (ELISA). The children were divided into different groups according to sex, age and geographical regions, and the distributional characteristics of allergens of the different groups were compared. Results: The overall positive rate for the 19 allergens of the 4 622 children was 62.8%. The ranking of the positive rates for individual allergens from high to low were as follows: 24.2% for milk, 18.0% for mold mix, 16.7% for dog dander, 16.4% for house dust mite, 11.7% for cat dander, 10.7% for cashew, 10.6% for weed pollen, 8.8% for egg white, 7.8% for house dust, 7.7% for tree pollen, 5.6% for amaranth, 4.9% for mulberry tree, 3.6% for mango, 3.2% for beef, 2.8% for cockroach, 2.1% for crab, 1.5% for shrimp, 0.8% for pineapple, and 0.3% for shellfish. Analysis based on sex showed that the allergen positive rates in boys were higher than those in girls. Analysis by age difference showed that generally the positive rates for inhaled allergens increased along with the increase in patient age, while the positive rates for ingested allergens decreased along with the increase in patient age. Analysis by geographical regions showed that the positive rate of house dust mite in the patients from the southern part of Shaanxi, the positive rate of weed pollen in the patients from the northern part of Shaanxi and the positive rates of milk and egg white in the patients from the central part of Shaanxi were higher than those in other areas. The cluster analysis and correlation analysis showed that the 19 allergens could be roughly divided into 4 categories. There were moderate correlations among tree pollen, mulberry tree and amaranth. There were moderate correlations among mulberry tree, mango and amaranth. There was moderate correlation between shrimp and crab, and there were mild or weak correlations among most of the other allergens. Conclusion: Among the 4 622 children with allergic diseases in Shaanxi Province who were treated in the Asthma Center, Department of Pediatrics, Xijing Hospital, male patients showed higher sensitivity to allergens. The positive rates of inhaled allergens increased, while the positive rates of ingested allergens decreased with increase in patient age. There were regional differences in the distribution of allergens. Some allergens were correlated with each other, which may be related to cross-reaction.


Assuntos
Asma , Hipersensibilidade , Alérgenos , Animais , Asma/epidemiologia , Gatos , Bovinos , Criança , Cães , Poeira , Humanos , Imunoglobulina E , Masculino
9.
Front Immunol ; 12: 731842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630412

RESUMO

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N 6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.

10.
Nano Lett ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633819

RESUMO

An aqueous electrolytic MnO2-Zn battery with eye-catching Mn2+/MnO2 cathode chemistry has been attracting immense interest for next-generation energy storage devices due to its irreplaceable advantages. However, the limited MnO2 conductivity restricts its long service life at high areal capacities. Here, we report a high-performance electrolytic MnO2-Zn battery via a bromine redox mediator, to enhance its electrochemical performance. The MnO2/Br2-Zn battery displays a high discharge voltage of 1.98 V with a capacity of ∼5.8 mAh cm-2. It also shows an excellent rate performance of 20 C with a long-term stability of over 600 cycles. Furthermore, the scaled-up MnO2/Br2-Zn battery with a capacity of ∼950 mAh exhibits a stable 100 cycles with a practical cell energy density of ∼32.4 Wh kg-1 and an attractively low energy cost of below 15 US$ kWh-1. The design approach can be generalized to other electrodes and battery systems, thus opening up new possibilities for large-scale energy storage.

11.
Plant Sci ; 312: 111024, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620429

RESUMO

Fruit coloration is an appearance trait that directly affects the commercial value and market competitiveness of apples. The red color of apple fruit is mainly affected by anthocyanin accumulation, and the synthesis of anthocyanin is affected by various factors. The critical roles of hormones and environmental factors during apple anthocyanin biosynthesis are described. This review also elaborates the specific mechanisms of the responses of internal genes to stress and changes in anthocyanin when apples are exposed to different environmental stressors. This study provides direction for future research on apple anthocyanin and is a reference for anthocyanin studies in other species.

12.
Appl Opt ; 60(23): 6837-6842, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34613163

RESUMO

We propose a new, to the best of our knowledge, compound technique to measure high-dynamic-range blood flow rate in a large-diameter vessel, which combines the dynamic scattering light (DLS) and the laser speckle contrast imaging (LSCI) methods, possessing the advantages of the high temporal resolution of DLS and the robust property of LSCI. By controlling the second-order spatial correlations of the laser speckle through two imaging systems, the speckle temporal intensity autocorrelation function g2(t) and the decorrelation time τc are directly measured using a high-speed camera. It turns out the enhanced spatial second-order correlation helps to measure the blood flow with higher dynamic range and that the measured parameter ß and the blood flow dynamics n were accurately determined. For further improvement the dynamic range, the modified LSCI method was adopted, and the decorrelation time as a function of blood flow rate was constructed. It reveals the feasibility of measuring the high flow rate in large-diameter vessels and provides significant guidance for the future biomedical study of the myocardial perfusion in coronary artery bypass grafting, ghost imaging, and ghost cytometry.

13.
Front Endocrinol (Lausanne) ; 12: 688654, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594300

RESUMO

Controlled ovarian stimulation (COS) is one of the most vital parts of in vitro fertilization-embryo transfer (IVF-ET). At present, no matter what kinds of COS protocols are used, clinicians have to face the challenge of selection of gonadotropin starting dose. Although several nomograms have been developed to calculate the appropriate gonadotropin starting dose in gonadotropin releasing hormone (GnRH) agonist protocol, no nomogram was suitable for GnRH antagonist protocol. This study aimed to develop a predictive nomogram for individualized gonadotropin starting dose in GnRH antagonist protocol. Single-center prospective cohort study was conducted, with 198 women aged 20-45 years underwent IVF/intracytoplasmic sperm injection (ICSI)-ET cycles. Blood samples were collected on the second day of the menstrual cycle. All women received ovarian stimulation using GnRH antagonist protocol. Univariate and multivariate analysis were performed to identify predictive factors of ovarian sensitivity (OS). A nomogram for gonadotropin starting dose was developed based on the multivariate regression model. Validation was performed using concordance statistics and bootstrap resampling. A multivariate regression model based on serum anti-Müllerian hormone (AMH) level, antral follicle count (AFC), and body mass index (BMI) was developed and accounted for 59% of the variability of OS. An easy-to-use predictive nomogram for gonadotropin starting dose was established with excellent accuracy. The concordance index (C-index) of the nomogram was 0.833 (95% CI, 0.829-0.837). Internal validation using bootstrap resampling further showed the good performance of the nomogram. In conclusion, gonadotropin starting dose in antagonist protocol can be predicted precisely by a novel nomogram.

14.
Orthop Surg ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605608

RESUMO

OBJECTIVE: To investigate the relief of low back pain after hip arthroplasty in patients with hip joint and spinal degenerative diseases, and to discuss the effects of unilateral and bilateral hip surgery on the relief of low back pain. METHODS: In this retrospective study, we followed 153 patients (69 males and 84 females, age: 43-88 years) who had undergone total hip arthroplasty (THA) via a posterolateral approach and also suffered from lumbar degenerative diseases in the period of 2009 to 2019. The inclusion criteria were: (i) patients who had been diagnosed with severe hip degenerative disease and also been diagnosed with lumbar degenerative disease; (ii) patients who had undergone THA surgery; and (iii) patients who were retrospectively recruited. The exclusion criteria were: (i) patients who had undergone lumbar fusion or internal fixation surgery; or (ii) patients who had vascular claudication, history of major trauma, diabetic polyneuropathy, lumbar and pelvic infections, tumor diseases; (iii) or patients who had undergone THA because of femoral neck fracture or ankylosing spondylitis. The improvement of hip joint function and the relief of low back pain (LBP) were studied, and the effect of unilateral and bilateral THA on the relief of LBP were discussed. Hip pain and function were evaluated by the Harris Hip Score (HHS), LBP was evaluated by Visual Analog Scale (VAS), and lumbar function was evaluated by the Japanese Orthopaedic Association (JOA) scoring system. RESULTS: The average follow-up time was 44.3 months (24-108 months). All patients recovered smoothly without complications. The LBP VAS of 153 patients decreased from 4.13 ± 1.37 preoperatively to 1.90 ± 1.44 postoperatively. The average HHS increased from 45.33 ± 13.23 preoperatively to 86.44 ± 7.59 postoperatively at the latest follow-up. According to Japanese Orthopaedic Association scoring system, the proportion of patients with good response to treatment in these 153 patients reached 93.46%. LBP VAS decreased from 4.18 ± 1.38 preoperatively to 1.95 ± 1.49 postoperatively in unilateral group and from 3.94 ± 1.32 preoperatively to 1.73 ± 1.23 postoperatively in bilateral group, respectively. There were only nine patients with persistent or aggravated LBP after operation. Among them, six patients underwent subsequent lumbar surgery (five patients had pain relieved after reoperation and one patient had not) and the other three patients chose conservative treatment for pain. CONCLUSION: THA can relieve LBP while relieving hip pain and restoring hip function in patients with both hip and lumbar degenerative disease, thus possibly avoiding further spinal surgery.

16.
Cell Rep ; 37(2): 109821, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34644569

RESUMO

Elevation in homocysteine (Hcy) level is associated with insulin resistance; however, the causality between them and the underlying mechanism remain elusive. Here, we show that Hcy induces insulin resistance and causes diabetic phenotypes by protein cysteine-homocysteinylation (C-Hcy) of the pro-insulin receptor (pro-IR). Mechanistically, Hcy reacts and modifies cysteine-825 of pro-IR in the endoplasmic reticulum (ER) and abrogates the formation of the original disulfide bond. C-Hcy impairs the interaction between pro-IR and the Furin protease in the Golgi apparatus, thereby hindering the cleavage of pro-IR. In mice, an increase in Hcy level decreases the mature IR level in various tissues, thereby inducing insulin resistance and the type 2 diabetes phenotype. Furthermore, inhibition of C-Hcy in vivo and in vitro by overexpressing protein disulfide isomerase rescues the Hcy-induced phenotypes. In conclusion, C-Hcy in the ER can serve as a potential pharmacological target for developing drugs to prevent insulin resistance and increase insulin sensitivity.

17.
Org Lett ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609892

RESUMO

An aerobic metal-free, visible-light-induced regioselective thiolation of phenols with thiophenols is reported. The cross-coupling protocol exhibits great functional group tolerance and high regioselectivity. Mechanistic studies reveal that the disulfide radical cation plays a crucial role in the visible-light catalysis of aerobic thiolation. Simply controlling the equivalent ratio of substrates enables the selective formation of sulfide or sulfoxide products with high activity in a one-pot reaction.

18.
Theranostics ; 11(19): 9605-9622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646389

RESUMO

Rationale: Recurrent and metastatic cancers often undergo a period of dormancy, which is closely associated with cellular quiescence, a state whereby cells exit the cell cycle and are reversibly arrested in G0 phase. Curative cancer treatment thus requires therapies that either sustain the dormant state of quiescent cancer cells, or preferentially, eliminate them. However, the mechanisms responsible for the survival of quiescent cancer cells remain obscure. Methods: Dual genome-editing was carried out using a CRISPR/Cas9-based system to label endogenous p27 and Ki67 with the green and red fluorescent proteins EGFP and mCherry, respectively, in melanoma cells. Analysis of transcriptomes of isolated EGFP-p27highmCherry-Ki67low quiescent cells was conducted at bulk and single cell levels using RNA-sequencing. The extracellular acidification rate and oxygen consumption rate were measured to define metabolic phenotypes. SiRNA and inducible shRNA knockdown, chromatin immunoprecipitation and luciferase reporter assays were employed to elucidate mechanisms of the metabolic switch in quiescent cells. Results: Dual labelling of endogenous p27 and Ki67 with differentiable fluorescent probes allowed for visualization, isolation, and analysis of viable p27highKi67low quiescent cells. Paradoxically, the proto-oncoprotein c-Myc, which commonly drives malignant cell cycle progression, was expressed at relatively high levels in p27highKi67low quiescent cells and supported their survival through promoting mitochondrial oxidative phosphorylation (OXPHOS). In this context, c-Myc selectively transactivated genes encoding OXPHOS enzymes, including subunits of isocitric dehydrogenase 3 (IDH3), whereas its binding to cell cycle progression gene promoters was decreased in quiescent cells. Silencing of c-Myc or the catalytic subunit of IDH3, IDH3α, preferentially killed quiescent cells, recapitulating the effect of treatment with OXPHOS inhibitors. Conclusion: These results establish a rigorous experimental system for investigating cellular quiescence, uncover the high selectivity of c-Myc in activating OXPHOS genes in quiescent cells, and propose OXPHOS targeting as a potential therapeutic avenue to counter cancer cells in quiescence.

19.
Biomed Pharmacother ; 143: 112238, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649362

RESUMO

OBJECTIVE: To gain a deeper understanding of the hot topics and future prospects of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors treatment of cancer through scientometric analysis of the top-100 most cited clinical trials. MATERIALS AND METHODS: We searched the Web of Science Core Collection database from 1980 to June 2019. Two reviewers independently screened the top-100 most cited clinical trials that defined by the National Institutes of Health starting from the most cited article. Title, year of publication, citations, type of cancer, and focused aspects of outcomes were extracted from included clinical trials. VOSviewer software (version 1.6.9) and Excel 2016 were used to do statistical analysis. The evidence mapping was used to present the relationship between cancers, drugs, citations, and outcomes, etc. RESULTS: The top-100 most cited clinical trials published from 2010 to 2018 in nine journals with high impact factor (IF) (IF2018:6.68-70.67), and Lancet Oncology (USA) published the most clinical trials (n = 29, IF2018 = 35.3856). The total number of citations of the top-100 most cited clinical trials was from 59 to 5606. 920 authors from 34 countries and 458 organizations participated in publishing the top-100 most cited clinical trials. The USA (n = 95) and Memorial Sloan-Kettering Cancer Center (n = 31) contributed the most publications. Based on the evidence mapping, there are 25 different types of cancers (e.g. lung cancer, melanoma, and renal cell cancer) and five focused aspects of outcomes (e.g. safety and efficacy). CONCLUSION: The USA was the dominant country. Anti-PD-1/PD-L1 drugs were widely used to treat lung cancer, melanoma, renal cell cancer, and Hodgkin lymphoma. More exploration should be done to explore the use of anti-PD-1/PD-L1 drugs to treat more type of cancers in future research.

20.
Enzyme Microb Technol ; 151: 109919, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649690

RESUMO

Improving enzyme stability is very important for enzyme applications. Structural modification is a reliable and effective method to improve the characteristics of protein. By artificially extending the C-terminus, 6 domain modification variants of different sizes were constructed, and a new enzyme species with high stability was obtained. Experimental results affirmed that high stability can be achieved by decreasing the degree of domain freedom. The optimum temperatures of domain modification variants were improved by 10 °C compared with the original enzyme. Specifically, compared with the original enzyme, the half-life of the variant dexYG-fdx (D-F) was increased to 280% under 35 °C and 200% under 45 °C, and the pH tolerance range was wider. Further structural simulations and molecular docking studies provided a reasonable explanation (The increased domain reduced the degree of freedom of the enzyme terminal to some extent) for this variant to increase stability and produce dextran. This study can provide valuable information for increasing the characteristics of recombinant dextransucrase.

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