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1.
Front Cell Dev Biol ; 10: 897096, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35656545

RESUMO

DNA repair mechanisms have been proven to be essential for cells, and abnormalities in DNA repair could cause various diseases, such as cancer. However, the diversity and complexity of DNA repair mechanisms obscure the functions of DNA repair in cancers. In addition, the relationships between DNA repair, the tumor mutational burden (TMB), and immune infiltration are still ambiguous. In the present study, we evaluated the prognostic values of various types of DNA repair mechanisms and found that double-strand break repair through single-strand annealing (SSA) and nonhomologous end-joining (NHEJ) was the most prognostic DNA repair processes in gastric cancer (GC) patients. Based on the activity of these two approaches and expression profiles, we constructed a HR-LR model, which could accurately divide patients into high-risk and low-risk groups with different probabilities of survival and recurrence. Similarly, we also constructed a cancer-normal model to estimate whether an individual had GC or normal health status. The prognostic value of the HR-LR model and the accuracy of the cancer-normal model were validated in several independent datasets. Notably, low-risk samples, which had higher SSA and NHEJ activities, had more somatic mutations and less immune infiltration. Furthermore, the analysis found that low-risk samples had higher and lower methylation levels in CpG islands (CGIs) and open sea regions respectively, and had higher expression levels of programmed death-ligand 1 (PD-L1) and lower methylation levels in the promoter of the gene encoding PD-L1. Moreover, low-risk samples were characterized primarily by higher levels of CD4+ memory T cells, CD8+ naive T cells, and CD8+ TEM cells than those in high-risk samples. Finally, we proposed a decision tree and nomogram to help predict the clinical outcome of an individual. These results provide an improved understanding of the complexity of DNA repair, the TMB, and immune infiltration in GC, and present an accurate prognostic model for use in GC patients.

2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(5): 533-537, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35728858

RESUMO

OBJECTIVE: To explore the accuracy of intelligent calculation (IC) method for risk assessment of hospitalization for patients, aiming to build a more advantageous risk assessment system. METHODS: The "Search Engine" program was developed based on hospital information system (HIS) of the Fifth Center Hospital in Tianjin, which automatically captured patient information and generated nutritional risk screening 2002 (NRS 2002) score, Caprini thrombosis risk assessment model and Padua thrombosis risk assessment model for venous thromboembolism (VTE), the CHA2DS2-VASc for predicting stroke risk stratification in atrial fibrillation and the HAS-BLED for predicting bleeding risk in anticoagulated patients with atrial fibrillation. A randomized controlled trial was conducted. According to the applicable conditions of each risk assessment, 100 risk scores from "Search Engine" program belonged to each risk assessment were randomly selected, defined as the IC group. Manual scoring with the data of the same case at the same time, defined as the traditional calculation (TC) group, compared the consistency of the scores and the difference in time-consuming between the two groups. RESULTS: The Bland-Altman plots showed that the 95% limits of agreement (95%LoA) of NRS 2002 score, Caprini score, Padua score, CHA2DS2-VASc score and HAS-BLED score was -0.46 to 0.41, -0.49 to 0.52, -0.50 to 0.41, -0.67 to 0.60, -0.44 to 0.43, respectively, all P > 0.05. In this study, the Bland-Altman plot showed that 95%, 96%, 97%, 97%, 95% plots fell within the 95%LoA in NRS 2002 score, Caprini score, Padua score, wwCHA2DS2-VASc score and HAS-BLED score by the two methods, respectively. The all plots of 95%LoA were within the clinically acceptable range (-0.5 to 0.5 scores). The time-consuming of NRS 2002 score, Caprini score, Padua score, CHA2DS2-VASc score and HAS-BLED score in IC group were significantly shorter than those in TC group [0.72 (0.71, 0.73) seconds vs. 361.02 (322.41, 361.02) seconds, 0.72 (0.72, 0.73) seconds vs. 196.68 (179.99, 291.20) seconds, 0.72 (0.72, 0.73) seconds vs. 105.75 (92.32, 114.70) seconds, 0.72 (0.71, 0.72) seconds vs. 72.66 (56.24, 84.20) seconds, 0.72 (0.71, 0.72) seconds vs. 51.30 (38.88, 57.15) seconds, respectively, all P < 0.001]. CONCLUSION: For the above five risk assessments, the TC method and IC method has good consistency in scores, and the IC method is faster, which has good application prospect for clinical application.

3.
Int Immunopharmacol ; 108: 108877, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35729844

RESUMO

OBJECTIVE: This study aimed to identify changes in T-cell factor-1 (TCF1) in circulating T-cell subsets of systemic lupus erythematosus (SLE) patients and to explore their significance in SLE. METHODS: Peripheral blood was collected from 41 SLE patients and 45 healthy controls (HCs). TCF1 in follicular helper T (TFH), follicular regulatory T (TFR) and regulatory T (Treg) cells was analyzed by flow cytometry. Interleukin-21 (IL-21), programmed death receptor 1 (PD-1) and killer cell lectin-like receptor G1 (KLRG1) were detected and compared among TFH subsets sorted according to TCF1 and CD62L expression. Correlation analyses were conducted between TCF1-related TFH cell subsets and autoantibody levels, systemic lupus erythematosus disease activity index (SLEDAI), and plasmablast levels of SLE patients. RESULTS: Absolute numbers of TCF1- TFH and TCF1+ Treg cells were increased in SLE patients. According to TCF1 and CD62L expression, circulating TFH cells and Tregs were sorted into four subsets. CD62L+TCF1+ TFH cell percentages were decreased, and CD62L-TCF1- TFH cells were increased. CD62L+TCF1+ Treg cell percentages were increased, and CD62L-TCF1- Treg cell percentages were decreased. KLRG1+ percentages in CD62L-TCF1-TFH were higher in SLE patients than in HCs. Functionally, CD62L+TCF1+ TFH cells had stronger IL-21 secretion, while CD62L-TCF1-TFH cells had weaker IL-21 secretion and lower PD-1 expression. TCF1- and CD62L-TCF1- TFH numbers were positively correlated with anti-ribosomal P, anti-dsDNA and SLEDAI. CONCLUSION: The increased TFH cells in SLE patients were mostly TCF1-negative subsets with weakened function. Changes in TCF1-related subsets can reflect the condition and abnormal humoral immunity of SLE patients.

4.
Front Pharmacol ; 13: 907826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721174

RESUMO

We characterized a so-called "heirloom recipe" Chinese herbal formula (temporarily named Formula X) that contains five Chinese medical botanical drugs, Huang-Lian (Coptis chinensis Franch. [Ranunculaceae]), Huang-Qin (Scutellaria baicalensis Georgi [Lamiaceae]), Bai-Wei (Vincetoxicum atratum (Bunge) C. Morren and Decne. [Apocynaceae]), E-Zhu (Curcuma aromatica Salisb. [Zingiberaceae]) and Bai-Zhu (Atractylodes macrocephala Koidz. [Asteraceae]). Formula X inhibited the growth of various cancer cells and decreased the expression levels of a panel of proteins, including CD133, Myc, PD-L1, and Slug, in cancer cells. We further found that the inhibition of growth and protein expression were exerted by Huang-Lian, Huang-Qin, and Bai-Wei (formula HHB), which exhibited the same biological effects as those of Formula X. Furthermore, we selected three active chemicals, berberine, baicalin, and saponin from Huang-Lian, Huang-Qin, and Bai-Wei, respectively, to produce a chemical formulation (formula BBS), which exhibited similar effects on cell growth and protein expression as those induced by formula HHB. Both the formulae HHB and BBS suppressed tumor growth in an animal study. Moreover, they decreased the protein levels of Myc and PD-L1 in tumor cells in vivo. In summary, we established a novel Chinese herbal formula and a chemical formula that targeted three important processes, tumor maintenance (tumor stem cells), progression, and metastasis, and that influenced the response of tumors to host immunosuppression, for the potentially effective treatment of cancer patients.

5.
World J Cardiol ; 14(5): 282-296, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35702326

RESUMO

BACKGROUND: Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated. AIM: To investigate the candidate genes and pathways involved in DCM patients. METHODS: Two expression datasets (GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between the DCM patients and healthy individuals were identified using the R package "linear models for microarray data." The pathways with common DEGs were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network (PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs (miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT. RESULTS: In total, 97 DEGs (47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in "response to growth factor," "extracellular matrix," and "extracellular matrix structural constituent." KEGG pathway analysis indicated that the DEGs were mainly enriched in "protein digestion and absorption" and "interleukin 17 (IL-17) signaling pathway." The PPI network suggested that collagen type III alpha 1 chain (COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells. CONCLUSION: COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM.

6.
Nat Prod Res ; : 1-7, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35722895

RESUMO

A new furanone analog, (E)-2-(8,9-dihydroxy-6,8-dimethyldec-4-en-2-yl)-met-hylfuran-3(2H)-one (1), together with six known compounds, including two diterpenoids (2 and 3), one butyrolactone (4) and three isocoumarins (5-7), were isolated from a deep-sea fungus, Purpureocillium sp. SCSIO 06693. Among them, compound 1 existed as two tautomeric forms (1a and 1b) differing in configuration of the furan ring. The chemical structures were elucidated by the basis of spectroscopic evidences, including HRESIMS, NMR and optical rotation. Isolated compounds were evaluated for their cytotoxic, antiviral, antibacterial, antioxidant, acetyl cholinesterase (AChE) and pancreatic lipase (PL) enzyme inhibitory activities. Biological evaluation results revealed that compound 4 showed modest antioxidant activity against DPPH with IC50 value of 72.03 µM. In addition, compounds 1-4 exhibited PL enzyme inhibitory activities.

7.
Biomed Res Int ; 2022: 5110161, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35707386

RESUMO

Alcoholic liver injury is a major global public health concern at present. The ADAM9 gene plays a crucial role in the occurrence and development of various liver diseases, but its role in acute alcoholic liver injury remains ambiguous. In this study, a chimeric single-guide RNA targeting the genomic regions of mouse ADAM9 was designed using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology. Next, the role of ADAM9 in acute alcoholic liver injury in vitro in cultured mouse cells and in vivo in a hydrodynamic injection-based alcoholic liver injury mouse model was documented. The findings of this study suggest that ADAM9 induces by regulating cell proliferation, apoptosis, and stress metabolism in mice. Thus, inhibiting the expression of ADAM9 gene using CRISPR/Cas9 can attenuate alcohol-induced acute liver injury in mice.


Assuntos
Sistemas CRISPR-Cas , RNA Guia , Animais , Células Cultivadas , Modelos Animais de Doenças , Edição de Genes , Fígado , Camundongos , RNA Guia/genética
8.
Front Endocrinol (Lausanne) ; 13: 852247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663308

RESUMO

Background: Hyperuricemia has recently been identified as a risk factor of cardiovascular diseases; however, prognostic value of hyperuricemia in patients with ST-segment elevation myocardial infarction (STEMI) remained unclear. Simultaneously, the mechanism of this possible relationship has not been clarified. At present, some views believe that hyperuricemia may be related to the inflammatory response. Our study aimed to investigate the association between hyperuricemia and long-term poor prognosis and inflammation in STEMI patients undergoing percutaneous coronary intervention (PCI). Methods: A total of 1,448 consecutive patients with STEMI were studied throughout 2013 at a single center. The primary endpoint was all-cause death at 2- and 5-year follow-up. Inflammatory biomarkers were collected on admission of those patients: high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count. Results: Hyperuricemia was associated with higher 2- and 5-year all-cause death in STEME patients compared to normouricemia (5.5% vs. 1.4%, P <0.001; 8.0% vs 3.9%, P = 0.004; respectively). After multivariable adjustment, hyperuricemia was still an independent predictor of 2-year all-cause death (hazard ratio (HR) =4.332, 95% confidence interval (CI): 1.990-9.430, P <0.001) and 5-year all-cause death (HR =2.063, 95% CI: 1.186-3.590, P =0.010). However, there was no difference in hs-CRP, ESR, and WBC count on admission in STEMI patients with hyperuricemia compared to normouricemia (P >0.05). Conclusions: Hyperuricemia was associated with higher risks of 2- and 5-year all-cause deaths in patients with STEMI undergoing PCI. However, this study did not find a correlation between hyperuricemia and inflammatory responses in newly admitted STEMI patients.


Assuntos
Hiperuricemia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Proteína C-Reativa/análise , Humanos , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do Tratamento
9.
Integr Zool ; 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35639924

RESUMO

The bicoid-related transcription factor 2 (Pitx2) plays a crucial role in the development of many organs and tissues by affecting the mitotic cell cycle. Postnatal testis development is related to mitosis and meiosis in multiple cell types, but the role of Pitx2 gene in seasonal inhibition of testicular development remains unknown in rodents. We analyzed PITX2 protein and Pitx2 mRNA expression features using both laboratory and wild male Rattus norvegicus caraco. In postnatal testicle of laboratory colony, we found that PITX2 was expressed in Leydig cells, pachytene spermatocytes, round spermatids, and elongating spermatids rather than spermatogonia and leptotene/zygotene spermatocytes. Pitx2b expression significantly increased along with the occurrence of pachytene spermatocytes and round spermatids, while decreased along with the processes of elongated spermatids. In wild male rats with similar testes weight, a significantly suppressed Pitx2b expression occurred with an active meiotic stage in the inhibited testes in autumn and winter, compared with the normally developing testes in spring and summer. These results indicate that Pitx2b expression suppression plays a crucial role in the seasonal inhibition of testis development. This article is protected by copyright. All rights reserved.

10.
Front Med (Lausanne) ; 9: 872881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572990

RESUMO

Background and Aims: Emergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB. Methods: Cirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed. Results: A total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively). Conclusion: The nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.

11.
J Exerc Sci Fit ; 20(3): 206-215, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35510253

RESUMO

Background/objective: Investigating the neural mechanisms underlying sport performance has been a research focus in the field of sport science. The current review aims to identify distinct characteristics between athletes and non-athletes at behavioral and neural levels. Further analysis was conducted as to potential reasons that contributed to the differences. Methods: Literature was searched through PubMed, ScienceDirect, Cochrane, EBSCO, and Web of Science for EEG studies that compared athletes with non-athletes or novices in behavioral performance and brain function. Results: The process of literature search and selection identified 16 studies that satisfied the predetermined inclusion criteria. Theta, alpha, and beta frequency bands were employed as the primary EEG measures of cortical activities in the included studies. Athletes indicated significant advantages over controls in behavioral performance, H e d g e s ' g = 0.42 , p = 0.02 , and brain function, H e d g e s ' g = 0.49 , p = 0.03 . Moderator analysis on behavioral performance indicated a large effect size in sport-related performance, H e d g e s ' g = 0.90 , p = 0.01 , but a small, non-significant effect size in general tasks, H e d g e s ' g = 0.14 , p = 0.44 . Conclusions: Superior performance in sport-related tasks mostly contributed to athletes' significant advantage in behavioral performance. Additionally, favorable profiles of brain function associated with athletes included neural efficiency, increased cortical asymmetry, greater cognitive flexibility, and precise timing of cortical activation. Applying EEG technique to sport has shown promising directions in performance improvement and talent identification for young athletes.

12.
Small ; : e2202400, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35587771

RESUMO

Coatings for passive radiative cooling applications must be highly reflected in the solar spectrum, and thus can hardly support any coloration without losing their functionality. In this work, a colorful daytime radiative cooling surface based on structural coloration is reported. A designed radiative cooler with a bioinspired array of truncated SiO2 microcones is manufactured via a self-assembly method and reactive ion etching. Complemented with a silver reflector, the radiative cooler exhibits broadband iridescent coloration due to the scattering induced by the truncated microcone array while maintaining an average reflectance of 95% in the solar spectrum and a high thermal emissivity (ε) of 0.95, owing to the reduced impedance mismatch provided by the patterned surface at infrared wavelengths, reaching an estimated cooling power of ≈143 W m-2 at an ambient temperature of 25 °C and a measured average temperature drop of 7.1 °C under direct sunlight. This strong cooling performance is attributed to its bioinspired surface pattern, which promotes both the aesthetics and cooling capacity of the daytime radiative cooler.

13.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35553615

RESUMO

BACKGROUND: Many drugs administered systemically suffer from drawbacks including off-target effects. One approach to address this limitation is tissue- or cell-targeted drug delivery, which can also improve therapeutic efficacy by increasing the "effective" dose. The goal of the current study was to develop a system to target a soluble epoxide hydrolase (sEH) inhibitor to the liver, since previous studies from our group and others demonstrated that elevated hepatic sEH contributes to the pathogenesis of liver diseases, including alcohol-associated liver disease (ALD). We tested the hypothesis that encapsulation of an sEH inhibitor in fusogenic lipid vesicles (FLVs) would enable liver targeting and ameliorate liver injury in a mouse model of ALD. METHODS: FLVs were constructed with unsaturated lipids 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate at a 3:2 molar ratio. FLVs were loaded with the sEH inhibitor t-TUCB at doses ranging from 0-9 mg/kg, then tagged with the fluorescent tracer DiD. Physical properties including size and zeta potential, as well as encapsulation efficiency were measured using a nanoparticle tracker analyzer and spectroscopy, respectively. To test the efficacy of t-TUCB-FLVs in vivo, we used a chronic-binge mouse model of ALD. Specifically, male C57BL/6 mice were fed a liquid diet containing ethanol for ten days followed by a single ethanol binge nine hours prior to sacrifice. t-TUCB-FLVs were administered by intraperitoneal injection two hours prior to the ethanol binge. We measured endpoints related to liver injury, steatosis, inflammation, cell death, and endoplasmic reticulum (ER) stress. One-way ANOVA was used to determine significance between groups (α = 0.05). RESULTS: Analysis of size, zeta potential, and encapsulation efficiency showed favorable physical characteristics for passively targeting t-TUCB-FLVs to the liver (129nm diameter, -55mV zeta potential, and 92% encapsulation efficiency). In a pilot dose response study, the presence of t-TUCB-FLVs in the liver was confirmed by fluorescent imaging and magnetic cell sorting followed by flow cytometry. In an experimental animal model, mice which received ethanol and 3.0 mg/kg t-TUCB-FLVs (observed to be the most effective dose) had significantly lower liver injury by plasma ALT levels compared to mice receiving ethanol and empty liposomes alone (47.75 U/L vs. 72.93 U/L, respectively). t-TUCB-FLV-treated mice also had decreased liver parenchymal cell death (by TUNEL staining) and markers of ER stress (Atf4, Atf6, and spliced Xbp1), with no significant effects on steatosis. CONCLUSIONS: We successfully developed a passive liver targeting system to deliver an sEH inhibitor to the liver in mice. In an ALD model, this drug formulation attenuated liver injury, cell death, and ER stress. This novel approach may help avoid clinical pitfalls which cause experimental drugs to fail in clinical trials, such as low efficacy or off-target side effects. Future research will further evaluate the mechanisms of t-TUCB-FLVs in ALD, evaluate potential side effects, and consider an active targeting approach.

14.
Front Mol Neurosci ; 15: 811441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359569

RESUMO

The role of the Slack (also known as Slo2.2, KNa1.1, or KCNT1) channel in pain-sensing is still in debate on which kind of pain it regulates. In the present study, we found that the Slack-/- mice exhibited decreased mechanical pain threshold but normal heat and cold pain sensitivity. Subsequently, X-gal staining, in situ hybridization, and immunofluorescence staining revealed high expression of the Slack channel in Isolectin B4 positive (IB4+) neurons in the dorsal root ganglion (DRG) and somatostatin-positive (SOM+) neurons in the spinal cord. Patch-clamp recordings indicated the firing frequency was increased in both small neurons in DRG and spinal SOM+ neurons in the Slack-/- mice whereas no obvious slow afterhyperpolarization was observed in both WT mice and Slack-/- mice. Furthermore, we found Kcnt1 gene expression in spinal SOM+ neurons in Slack-/- mice partially relieved the mechanical pain hypersensitivity of Slack-/- mice and decreased AP firing rates of the spinal SOM+ neurons. Finally, deletion of the Slack channel in spinal SOM+ neurons is sufficient to result in mechanical pain hypersensitivity in mice. In summary, our results suggest the important role of the Slack channel in the regulation of mechanical pain-sensing both in small neurons in DRG and SOM+ neurons in the spinal dorsal horn.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 583-592, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35396001

RESUMO

OBJECTIVE: To investigate the changes of gene sequencing and proteomics of apheresis platelet (AP) exosomes in different storage periods and predict the function of AP exosomes in different storage periods. METHODS: Platelets at different storage periods of 0 day (D0), 3 day (D3) and 5 day (D5) were collected, exosomes were extracted with Gradient centrifugation; gene sequencing and proteomic analysis were used to analyze the exosomes, and biological functions of platelet exosomes were analyzed and predicted by bioinformatics. Liquid mass spectrometry (LMS) was used to detect the changes and function prediction of exosomes proteins. The small RNA sequencing library was prepared, and the constructed library was sequenced and bioinformatics technology was used for data analysis. RESULTS: AP exosome iTRAQ protein analysis showed that AP exosomes stored in D3 with 55 up-regulated proteins and 94 down-regulated proteins (P<0.05, FC<0.83 or FC>1.2), while AP exosomes stored in D5 with 292 up-regulated proteins and 53 down-regulated proteins (P<0.05, FC<0.83 or FC>1.2) as compared with D0. KEGG pathway analysis showed that the proteins were mainly involved in transport and metabolism, immune system, cancer, membrane transport and other processes. There were statistically significant differences between AP exosome miRNAs in different storage days (P<0.01). The number of miRNA up-regulated and down-regulated was 374 and 255 as compared with the number of platelet exosomes miRNA stored in D3 and D0, while that was 297 and 242 in D5 and D0, and 252 and 327 in D5 and D3, respectively. The target genes of differential platelet exosome miRNAs were analyzed by GO enrichment. Target genes of differential miRNA were mainly involved in membrane composition, mainly played molecular functions binding to proteins, and participated in biological processes of transcriptional regulation. CONCLUSION: The exosome differential proteins and miRNAs in D5 are significantly different from those in the D0 of APs, and they are involved in various biological processes.


Assuntos
Remoção de Componentes Sanguíneos , Exossomos , MicroRNAs , Plaquetas/metabolismo , Exossomos/genética , Exossomos/metabolismo , Humanos , MicroRNAs/genética , Proteômica
16.
Immunol Invest ; : 1-16, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35404706

RESUMO

OBJECTIVE: This study aims to elucidate the changes in the percentage of GPR56 and/or granzyme B (GZMB) positive cells in rheumatoid arthritis (RA) CD4 and CD8 T lymphocytes, and to explore their clinical value in diagnosing and reflecting the progression of RA. METHODS: The percentages of GPR56 and/or GZMB positive cells were analyzed in peripheral blood (PB) and spleen T cells in a collagen-induced arthritis (CIA) model established in DBA/1 mice. The percentages of GPR56+ and/or GZMB+ cells were further analyzed in PBs from RA patients and healthy controls. Correlation analysis was performed between clinical indicators and GPR56+, GZMB+, and GPR56+ GZMB+ T cells. Receiver operating characteristic (ROC) curves were used to evaluate the value of GPR56 and GZMB in differentiating active and stable remitting RA. RESULTS: GPR56+ levels were increased in CD4 and CD8 T cells in the PB of CIA mice. The percentages of GPR56+ and GZMB+ cells were increased in both CD4 and CD8 T cell subsets in patients with active RA. GPR56+, GZMB+, and GPR56+ GZMB+ cells were positively correlated with rheumatoid factor and DAS28. ROC analysis revealed that AUCs for GPR56+, GZMB+, and GPR56+ GZMB+ cell percentages to distinguish active RA from stable remission RA were 0.7106, 0.6941, 0.7024, with cut-off values of 16.35, 16.40, 14.80 in CD4 + T cells, and 0.8031, 0.8086, 0.8196 with cut-off values 60.25, 62.15, 40.15 in CD8 + T cells, respectively. CONCLUSIONS: GPR56+ and/or GZMB+ T cells are up-regulated in patients with active RA and reflect their condition. The detection of GPR56 and GZMB is helpful for RA disease assessment.

17.
Pest Manag Sci ; 78(6): 2704-2713, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35394111

RESUMO

BACKGROUND: Some rodent species living in arid areas show elevated physiological tolerance to anti-vitamin K rodenticides (AVKs), which seems to be due to some unknown selective pressures that rodents may experience in desert habitats. Genes involved in the ϒ-carboxylation of blood coagulation, including vitamin K epoxide reductase complex, subunit 1 (Vkorc1), ϒ-glutamyl-carboxylase (Ggcx) and NAD(P)H quinone one dehydrogenase (Nqo1) are associated with anticoagulant resistance, or some levels of elevated tolerance, in rodents. To detect whether the DNA sequences of the three genes are also under natural selection in the desert rodent species, we analyzed the Vkorc1, Ggcx and Nqo1 genes of the desert rodents and compared them with other rodent species. RESULTS: We found an accelerated evolutionary rate in Vkorc1 of desert rodents, especially in Mus spretus, Nannospalax galili and Psammomys obesus. By contrast, signals of positive selection were absent for Ggcx and Nqo1 in all species. Mapping the amino acid variations on the VKORC1 protein three-dimensional model suggested most interspecific amino acid variations occur on the outer surface of the VKORC1 pocket, whereas most intraspecific amino acid changes and known AVK resistance mutations occurred on the inner surface and endoplasmic reticulum luminal loop regions. Some desert-species-specific amino acid variations were found on the positions where known resistance mutations occurred, indicating these variations might be related to the elevated physical tolerance to AVKs in desert rodents. CONCLUSION: The evolution of Vkorc1 has been accelerated in some desert rodent species, indicating genetic preadaptation to anticoagulant rodenticides. Positive selection and relaxed selection have been detected in Psammomys obesus and Nannospalax galili, indicating the two rodent species might also show tolerance to AVKs, which needs further verification. © 2022 Society of Chemical Industry.


Assuntos
Rodenticidas , Aminoácidos , Animais , Anticoagulantes/farmacologia , Proteínas de Membrana/genética , Camundongos , Roedores/genética , Rodenticidas/farmacologia , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo
18.
ACS Appl Mater Interfaces ; 14(18): 21613-21622, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35482585

RESUMO

The application of flexible indium tin oxide (ITO)-free electrochromic devices (FCDs) has always been a research hotspot in flexible electronics. Recently, a silver nanowire (AgNW)-based transparent conductive film has raised great interest as an ITO-free substrate for FCDs. However, several challenges, such as the weak binding of AgNWs to the substrate, high junction resistance, and oxidation of AgNWs, remain. In this paper, a novel method for surface modification of AgNWs with N-aminoethyl-γ-aminopropyltrimethoxysilane [Si(NH2)] solution is proposed to enhance the bonding with the flexible substrates and the active materials, thereby inhibiting the delamination of AgNWs from the substrate and reducing the high junction resistance between nanowires. The TiO2/AgNW-Si(NH2)/poly(ethylene terephthalate) (PET) films show outstanding mechanical properties, of which the resistance remains almost unchanged after mechanical bending of 5000 cycles (ΔR/R0 ≈ 3.6%) and repeated peeling off cycles with 3M tape 100 times (ΔR/R0 ≈ 6.0%). In addition, we found that the oxygen-containing groups on the TiO2/AgNW-Si(NH2)/PET surface form hydrogen bonds with the TiO2 sol, resulting in tight contact between the TiO2 sol and the AgNWs, which prevents the AgNWs from oxidation. As a result, the TiO2/AgNW-Si(NH2)/PET film exhibited long-time aging (ΔR/R0 ≈ 4.9% in the air for 100 days) stability. A FCD was constructed with the TiO2/AgNW-Si(NH2)/PET film, which showed excellent electrochromic performance (94% retention) after 5000 bending cycles, indicating high stability and mechanical flexibility. These results present a promising solution to the transparent conductive films for flexible energy devices.

19.
Dalton Trans ; 51(16): 6358-6365, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35383821

RESUMO

Reactions of [Et4N][Tp*WS3(CuCl)3] (1) (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate) with 2 equiv. of AgOTf (OTf- = trifluoromethanesulfonate) and 1 equiv. of several bidentate pyridine ligands including 2,5-bis(pyridine-4-yl)thiazolo[5,4-d]thiazole (L1), 2,7-di(pyridin-4-yl)-9H-fluorene (L2), 2,7-di(pyridin-4-yl)-9H-carbazole (L3), and 2,7-di(pyridin-4-yl)-9H-fluoren-9-one (L4) afforded four W/Cu/S cluster-based supramolecular compounds [(Tp*WS3Cu2Cl)2(L1)] (2), {[(Tp*WS3Cu3)2(µ-Cl)2(µ4-Cl)]2(L2)2}(OTf)2 (3), {[(Tp*WS3Cu3)2(µ-Cl)2(µ4-Cl)]2(L3)2}(OTf)2 (4) and {[(Tp*WS3Cu3)2(µ-Cl)2(µ4-Cl)]2(L4)2}(OTf)2 (5). Compounds 2-5 were characterized by elemental analysis, IR, UV-vis, 1H NMR, and single-crystal X-ray diffraction analysis. The neutral cluster 2 behaves as a supramolecular wire constructed by L1 bridging two butterfly-shaped [Tp*WS3Cu2Cl] cores. The cluster cations of 3-5 contain two [(Tp*WS3Cu3)2(µ-Cl)2(µ4-Cl)]+ cores linked by two L2, L3, or L4 ligands, which finally formed a cationic supramolecular rectangle. The third-order nonlinear-optical (NLO) properties of 3-5 in DMF were also investigated by Z-scan techniques and their NLO responses were enhanced compared to those of their precursor 1.

20.
Carbohydr Polym ; 288: 119400, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35450652

RESUMO

TiO2-based materials have been developing rapidly as eco-friendly photocatalysts, but the inherent defects limited their application, such as rapid recombination of photogenerated electrons and wide bandgap. To obtain high-efficient TiO2/carbonaceous photocatalysts (TiO2/C), we prepared the nanocomposite by carbonizing titanium alginate coordination compound and studied their photocatalytic performance against methylene blue (MB) under simulated sunlight irradiation. The resultant nanocomposites were characterized by FT-IR, XPS, XRD, SEM-EDS, TG-DTG, UV-DRS, and N2 adsorption-desorption analysis. The carbon mainly existed in the outer layer of TiO2/C composites, contributing to the optical sensibilization. As a result, the degradation efficiency of sample TiO2/C-20 to MB could reach 97.47% within 15 min under simulated sunlight. The samples also possessed high stability, proved by the 0.72% reduction in photodegradation ratio after five cyclic tests. The present study proved the feasibility of preparing photocatalyst from titanium-alginate coordination compound and provided an extensible approach for preparing high-efficiency photocatalysts from a polysaccharide-based coordination compound.


Assuntos
Nanocompostos , Titânio , Alginatos , Catálise , Azul de Metileno , Nanocompostos/efeitos da radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio/efeitos da radiação
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