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1.
Front Endocrinol (Lausanne) ; 12: 701253, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234746

RESUMO

Objective: We aim to assess the accuracy of near infrared autofluorescence in identifying parathyroid gland during thyroid and parathyroid surgery. Method: A systematic literature search was conducted by using PubMed, Embase, and the Cochrane Library electronic databases for studies that were published up to February 2021. The reference lists of the retrieved articles were also reviewed. Two authors independently assessed the methodological quality and extracted the data. A random-effects model was used to calculate the combined variable. Publication bias in these studies was evaluated with the Deeks' funnel plots. Result: A total of 24 studies involving 2,062 patients and 6,680 specimens were included for the meta-analysis. The overall combined sensitivity and specificity, and the area under curve of near infrared autofluorescence were 0.96, 0.96, and 0.99, respectively. Significant heterogeneities were presented (Sen: I2 = 87.97%, Spe: I2 = 65.38%). In the subgroup of thyroid surgery, the combined sensitivity and specificity, and the area under curve of near infrared autofluorescence was 0.98, 0.99, and 0.99, respectively, and the heterogeneities were moderate (Sen: I2 = 59.71%, Spe: I2 = 67.65%). Conclusion: Near infrared autofluorescence is an excellent indicator for identifying parathyroid gland during thyroid and parathyroid surgery.

2.
Cell Res ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34239070

RESUMO

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34231152

RESUMO

Fine particulate matter (PM2.5) is still the primary air pollutant in most Chinese cities and its adverse effects on lung function have been widely reported. However, short-term effects of individual exposure to PM2.5 on pulmonary expiration flow indices remain largely unknown. In this study, we examined the short-term effects of real-time individual exposure to PM2.5 on lung function in a panel of 115 healthy adults. We measured individual real-time PM2.5 exposure and lung function. Environmental PM2.5 concentrations in the same period were collected from the nearest monitoring station. Generalized linear model was used to assess the effects of individual PM2.5 exposure on lung function after adjusting for potential confounders. Individual PM2.5 exposure ranged from 18.5 to 42.4 µg/m3 with fluctuations over time and ambient PM2.5 concentrations presented a moderate trend of fluctuation at the same day. Except forced expiratory volume in 1 s (FEV1) decline related to 2-h moving average PM2.5 exposure, no significant associations between individual PM2.5 exposure and other volume indices including forced vital capacity (FVC) and FEV1/FVC ratio were observed. The adverse effects of individual PM2.5 exposure on pulmonary expiration flow indices including peak expiratory flow (PEF), maximal mid-expiratory flow (MMF) and forced expiratory flow at 50%, and 75% of vital capacity (FEF50% and FEF75%) were observed to be strongest at 2 moving average hours and could last for 24 h. Stratified analysis showed greater and longer effects among participants who were aged over 40 years, males, or smokers. These findings suggested that individual PM2.5 exposure was significantly associated with altered lung function, especially with pulmonary expiration flow indices decline, which was strongest at 2 moving average hours and could last for 24 h.

4.
Plant Dis ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232054

RESUMO

Corydalis acuminata Franch., C. edulis Maxim. and C. racemosa (Thunb.) Pers. of family Papaveraceae are rich in multiple alkaloids and widely used as Chinese medicinal herbs, for treating cough, pruritus, sores tinea and snake venom (Zhang et al. 2008, Iranshahy et al. 2014). In April 2021, orange rust pustules were observed on C. acuminata, C. edulis and C. racemosa in Shaanxi Province (34°4'56'' N, 108°2'9'' E, alt. 770 m), China. Samples were collected and voucher specimens were preserved in the Herbarium Mycologicum Academiae Sinicae (nos. HMAS249947-HMAS249949), China. Consequent geospatial investigations revealed that diseased plants can be observed at an altitude of 400-1000 m, and show an incidence from 40% to 80% varied by altitude. Spermogonia epiphyllous, subcuticular, densely grouped, oval or round, 0.14-0.36 × 0.09-0.30 mm, pale orange-yellow, and type 3 of Cummins and Hiratsuka (1963). Aecia mostly hypophyllous, subepidermal without peridia, Caeoma-type, erumpent, densely grouped, oval or round, 0.27-0.85 × 0.15-0.43 mm, and orange-yellow; hyaline peridial cells produced in a periphery of the sorus under the ruptured epidermis of host plants. Aeciospores globoid or broadly ellipsoid, catenulate with intercalary cells, 15.7-20.1 × 10.8-15.7 µm, yellow to pale orange; walls hyaline, verrucose, 1.7-3.1 µm thick. This fungus was morphologically identified as Melampsora (Melampsoraceae). The rDNA-28S and the internal transcribed spacer (ITS) regions were amplified using primers NL1/NL4 and ITS1/ITS4 (Ji et al. 2020; Wang et al. 2020). Bi-directional sequences were assembled and deposited in GenBank (accession nos. MW990091-MW990093 and MW996576-MW996578). Phylogenetic trees were constructed with the ITS+rDNA-28S dataset based on maximum-likelihood (ML), maximum-parsimony (MP) and Bayesian Inference (BI). ML and MP bootstrap values were calculated by bootstrap analyses of 1,000 replicates using MEGA-X (Kumar et al. 2018), while BI posterior probabilities (Bpps) were calculated using MrBayes ver. 3.1.2 (Ji et al. 2020; Wang et al. 2020). Phylogenetic analyses grouped our specimens and Melampsora ferrinii Toome & Aime into one clade, highly supported by bootstrap values of ML, MP, and Bpps of 100%/100%/1. Inoculations were conducted with 1-year-old plants of original host, Salix babylonica L. (Toome & Aime 2015). Aeciospores suspension with a concentration of 106 spores/ml were sprayed on 20 healthy leaves, with another 20 healthy leaves sprayed with sterile water as the control. The inoculated plants were kept in darkness at 20-25 °C for 2 days and then transferred into greenhouse at 23°C with 16 h light per day. After 8-10 days of inoculation, yellow pustules of uredinia appeared on abaxial surfaces of the inoculated leaves, which were identical to Toome & Aime (2015) reported, while the control leaves remained healthy. Inoculations with the same method were conducted by spraying urediniospores, and the same rust symptoms developed after 8 days. Genus Corydalis was verified as the alternate host of M. chelidonii-pierotii Tak. Matsumoto, M. coleosporioides Dietel, M. idesiae Miyabe and M. yezoensis Miyabe & T. Matsumoto (Shinyama & Yamaoka 2012; Okane et al. 2014; Yamaoka & Okane 2019), and C. incisa (Thunb.) Pers. was speculated as the potential alternate host of M. ferrinii (Toome & Aime 2015). Based on morphology, phylogeny and pathogenicity, we firstly report M. ferrinii in mainland China and verify C. acuminata, C. edulis and C. racemosa instead of C. incisa as its alternate hosts.

5.
Nanomedicine ; : 102440, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34256062

RESUMO

Lately, chemotherapy and photodynamic therapy (PDT) synergistic therapy has become a promising anti-cancer treatment mean. However, the hypoxia in tumor leads to huge impediments to the oxygen-dependent PDT effects. In this work, a multifunctional nanoplatform (TUDMP) based a multivariable porphyrin-nMOFs core and a manganese dioxide (MnO2) shell was prepared for relieving tumor hypoxia and enhancing chemo-photodynamic synergistic therapy performance. The obtained TUDMP nanoplatform could effectively catalyze the hydrolysis of hydrogen peroxide to generate oxygen and also lead to consumption of antioxidant GSH, thereby facilitates the production of cytotoxic reactive oxygen species (ROS) by photosensitizer under laser irradiation. More importantly, the decomposition of the MnO2 shell would further promote the release of the loaded doxorubicin (DOX), and thus an efficient chemo-PDT synergistic therapy was realized. Both in vitro and in vivo experimental results demonstrated the oxygen self-sufficient multifunctional nanoplatform could exhibited significantly enhanced anticancer efficiencies compared with chemotherapy or PDT alone.

6.
Pathol Oncol Res ; 27: 1609753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257614

RESUMO

Background: Chemotherapy failure causes high breast cancer recurrence and poor patient prognosis. Thus, we studied a cohort of novel biomarkers to predict chemotherapeutic response in breast cancer. In this study, miRNA expression profiling was performed on 10 breast cancer punctured specimens sensitive to chemotherapy (MP grade 4, 5) and 10 chemotherapy resistant (MP grade 1). Differentially expressed miRNAs were verified by qRT-PCR in 60 initial samples, 59 validated samples and 71 independent samples. A miRNA signature was generated using a Logistic regression model. A receiver operating characteristic (ROC) test was used to assess specificity and sensitivity of single miRNA and miRNA signature. Target genes regulated by miRNAs and their involved signaling pathways were analyzed using GO enrichment and KEGG software. MiRNAs expression were separately compared with ER, PR, HER2 immunohistochemical staining and different drugs. qRT-PCR showed that the high expression of miR-23a-3p, miR-200c-3p, miR-214-3p and the low expression of miR-451a and miR-638 were closely related to chemoresistance. According to the formula for calculating the drug resistance risk, patients in the high-risk group were more likely to develop chemotherapy resistance than the low-risk group. Bioinformatics analysis showed that 5 miRNAs and target genes are mainly involved in p53, ubiquitin-mediated proteolysis, mTOR, Wnt, cells skeletal protein regulation, cell adhesion and ErbB signaling pathways. miR-451a expression was associated with ER, HER-2 status and anthracyclines. A miRNA signature of chemotherapeutic response may be clinically valuable for improving current chemotherapy regimens of individual treatment for patients with breast cancer.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34258777

RESUMO

BACKGROUND AND AIM: Regorafenib is a potent multi-kinase inhibitor for the second-line targeted therapy against hepatocellular carcinoma (HCC), however drug resistance is emerging in clinical settings. Although cancer stem cells (CSCs) are considered as key determinate of drug sensitivity, it remains unclear how CSCs may communicate with the differentiated counterparts (non-CSC) to dictate therapeutic efficacy. Therefore, we sought to investigate the Regorafenib resistance mechanism of CSCs in HCC. METHODS: We used sphere formation and soft agar colony formation assays to evaluate the stemness capacity of cancer cells. Cell viability assay was performed to detect the sensitivity of cancer cells to Regorafenib. Real-time quantitative PCR and western blot were used to analyze gene expression. Mouse xenograft tumor model was performed to assess Regorafenib sensitivity in vivo. RESULTS: Exosomes are highly enriched in CSC supernatant compared to that of non-CSC. And RAB27A mediates exosome secretion from CSCs to maintain stem-like phenotype and Regorafenib insensitivity. Moreover, exosomes released by CSCs up-regulate the expression of Nanog in non-CSC, while depleting Nanog sensitizes non-CSC to Regorafenib in the presence of CSC exosomes. Consistently, analysis of TCGA datasets reveals that RAB27A expression tightly correlates with Nanog in HCC tissues. More importantly, Depletion of RAB27A down-regulates Nanog expression and sensitizes cancer cells to Regorafenib in nude mice. CONCLUSIONS: Our findings suggest that CSCs release exosomes in a RAB27A-dependent manner to induce Nanog expression and Regorafenib resistance in differentiated cells, targeting this exosome signaling between distinct cellular subsets may be a potential therapeutic strategy for HCC patients.

8.
Orphanet J Rare Dis ; 16(1): 314, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266467

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) for the treatment of malignant infantile osteopetrosis (MIOP) and intermediate osteopetrosis. METHODS: Children with MIOP and IOP who underwent haplo-HSCT in Beijing Children's Hospital, Capital Medical University, from January 2010 to May 2018 were retrospectively analysed. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. RESULTS: Twenty-seven patients, including 18 males and 9 females, with an onset age of 12 (0.04-72) months were enrolled in this study. The median time from diagnosis to transplantation was 4 (1-23) months. All patients received haplo-HSCT with a myeloablative conditioning regimen (including fludarabine, busulfan, and cyclophosphamide). Graft versus host disease (GVHD) prophylaxis was based on anti-human T lymphocyte porcine immunoglobulin/anti-human thymus globulin, methotrexate, and mycophenolate mofetil. The median observation time was 55.2 (0.3-126.2) months. By the end of follow-up, twenty patients survived and seven patients died. The 5 year overall survival rate was 73.9%. Stage I-II acute GVHD was observed in 20 patients, stage III GVHD in 1 patient and no patients had stage IV disease. Chronic GVHD was observed in 11 patients (40.7%) and was controlled by anti-GVHD therapy. CONCLUSIONS: Haplo-HSCT was an effective treatment for MIOP and IOP, with a high survival rate and significantly improved clinical symptoms. For patients with a vision impairment before HSCT, the improvement was slow after transplantation. The incidence of GVHD was high but mild and was effectively controlled by appropriate treatment. These data indicated that haplo-HSCT was a feasible treatment for MIOP and IOP.

9.
Protein Expr Purif ; : 105933, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34273541

RESUMO

Zearalenone (ZEN), one of the most dangerous mycotoxins, causes enormous economic losses in the food and feed industries. To solve the problem of ZEN pollution, ZEN detoxifying enzymes are in emergent need. In this study, a zearalenone lactonohydrolase from Trichoderma aggressivum, denoted as ZHD-P, was heterologously expressed and characterized. The intracellular ZHD-P from E. coli BL21(DE3) exhibited high activity for ZEN degradation (191.94 U/mg), with the optimal temperature and pH of 45 °C and 7.5-9.0, respectively. With excellent temperature stability, the intracellular ZHD-P retained 100% activity when it was incubated at 25-40 °C for 1 h. Furthermore, we firstly constructed an E. coli cell surface display system for ZHD-P. The surface-displayed ZHD-P exhibited high activity against ZEN and showed optimal activity at 40 °C and pH 9.0. With superior pH stability, the surface-displayed ZHD-P retained 80% activity when it was incubated at pH 5.0-11.0 for 12 h. Interestingly, the metal ions tolerance of the surface-displayed ZHD-P was better than the intracellular form. Additionally, the surface-displayed ZHD-P could be reused four times with the residual enzyme activity of more than 50%. The biotoxicity assessment using P. phosphoreum T3 indicated that ZEN could be degraded into hypotoxic products by the intracellular or surface-displayed ZHD-P. ZHD-P could be feasible for ZEN detoxification.

10.
Anticancer Drugs ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34261910

RESUMO

Brain metastasis is one of the common distant metastases of lung cancer. The prognosis of patients with brain metastasis is worse and the survival time is shorter. In this report, we described a rare mutation of EGFR G2607A (rs1050171) in two patients over 50 years of age with brain metastasis of lung cancer. These two patients were both treated with afatinib, followed up for 13 months and 45 months respectively. Both patients showed that the tumor subsided, the curative effect was identified as partial response (PR), no recurrence and progress occurred and still being under follow-up. Our study provides a support that afatinib may be a reasonable therapeutic option for patients with brain metastasis of lung cancer.

11.
Plant J ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252236

RESUMO

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 megabases) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. We obtained a total of 5,818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: 'missing a small part' in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein that is specifically required for iron transport. Increased accumulation of iron and ROS as well as ferroptosis-like cell death were detected in endosperm of qk1. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.

12.
Sci Total Environ ; 795: 148616, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34252773

RESUMO

Nitrogen nutrient surplus is the main cause of a series of environmental problems in the Yangtze Estuary and its adjacent East China Sea (ECS). Denitrification plays an important role in controlling nitrate dynamics and fate in estuarine and coastal environments. We investigated the natural and potential rates of denitrification in the sediments of the Yangtze Estuary and ECS via slurry incubation experiments combined with acetylene inhibition techniques to reveal its contributions to total nitrogen reduction in this hypereutrophic continental shelf area. Key environmental factors, such as the sediment grain size, sediment extractable inorganic nitrogen (NH4+, NO3- and NO2-), sediment organic carbon (SOC), total nitrogen (TN), isotopic compositions (δ13C and δ15N), etc., were also investigated to determine the main factors controlling the denitrification processes. The measured rates of denitrification ranged from 0.39 to 28.49 ng N g-1·h-1. The total nitrogen removed by denitrification in the study area was 3.7 × 1010 g during August. In total, at least 3.3% of the external inorganic nitrogen transported annually into the estuary could be removed by the denitrification processes in the study area. The sediment denitrification rates correlated significantly with the extractable ammonium and δ15N values of surface sediments, indicating that coupled nitrification-denitrification processes may play an important role in nitrogen removal. Almost undetectable levels of nitrate in the sediment further revealed that nitrate supply, regardless of diffusion from the overlying water or production by sediment nitrification processes, is the bottleneck for denitrification.

13.
Aging (Albany NY) ; 13(undefined)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252883

RESUMO

Cadherin-23(CDH23) mediates homotypic and heterotypic cell-cell adhesions in cancer cells. However, the epigenetic regulation, the biological functions, the mechanisms and the prognostic value of CDH23 in diffuse large B-cell lymphoma (DLBCL) are still unclear. The Gene Expression Profiling Interactive Analysis (GEPIA) and the Gene Expression Omnibus (GEO) database were employed to analyze the CDH23 expression level in DLBCL. The correlation of CDH23 expression and methylation was analyzed by LinkedOmics database. The prognostic value was analyzed via GEPIA. Correlated genes, target kinase, target miRNA, target transcription factor and biological functions were identified by LinkedOmics and GeneMANIA database. The relationship between CDH23 and the immune cell infiltration was explored by the Tumor Immune Estimation Resource (TIMER). The expression of CDH23 was reduced by DNA methylation significantly in DLBCL tissue. Reduction of CDH23 represented poor outcome of DLBCL patients. Functional enrichment analysis showed that CDH23 mainly enriched in cancer cell growth, cell metastasis, cell adhesion, cell cycle, drug catabolic process, leukocyte mediated immunity and DNA repair by some cancer related kinases, miRNAs and transcription factors. These results indicated that methylated reduction of CDH23 represented poor outcome of DLBCL. CDH23 is associated with essential biological functions and key molecules in DLBCL. CDH23 may play crucial roles in DLBCL tumorigenesis. Our results lay a foundation for further investigation of the role of CDH23 in DLBCL tumorigenesis.

14.
Nat Commun ; 12(1): 4373, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272385

RESUMO

Although homologous recombination (HR) is indicated as a high-fidelity repair mechanism, break-induced replication (BIR), a subtype of HR, is a mutagenic mechanism that leads to chromosome rearrangements. It remains poorly understood how cells suppress mutagenic BIR. Trapping of Topoisomerase 1 by camptothecin (CPT) in a cleavage complex on the DNA can be transformed into single-ended double-strand breaks (seDSBs) upon DNA replication or colliding with transcriptional machinery. Here, we demonstrate a role of Abraxas in limiting seDSBs undergoing BIR-dependent mitotic DNA synthesis. Through counteracting K63-linked ubiquitin modification, Abraxas restricts SLX4/Mus81 recruitment to CPT damage sites for cleavage and subsequent resection processed by MRE11 endonuclease, CtIP, and DNA2/BLM. Uncontrolled SLX4/MUS81 loading and excessive end resection due to Abraxas-deficiency leads to increased mitotic DNA synthesis via RAD52- and POLD3- dependent, RAD51-independent BIR and extensive chromosome aberrations. Our work implicates Abraxas/BRCA1-A complex as a critical regulator that restrains BIR for protection of genome stability.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34275277

RESUMO

Nanopapers derived from nanofibrillated cellulose (NFC) are urgently required as attractive substrates for thermal management applications of electronic devices because of their lightweight, easy cutting, cost efficiency, and sustainability. In this paper, we provided a facile fabrication strategy to construct hybrid nanopapers composed of dialdehyde nanofibrillated cellulose (DANFC) and silver nanoparticles (AgNPs), which exhibited a favorable thermal conductivity property. AgNPs were in situ proceeded on the surface of DANFC by the silver mirror reaction inspired by the aldehyde groups. Owing to the intermolecular hydrogen bonds inside the hybrid nanopapers, the DANFC enables the uniform dispersion of AgNPs as well as promotes the formation of the hierarchical structure. It was found that the AgNPs-coated DANFC (DANFC/Ag) hybrid nanopapers could easily form an effective thermally conductive pathway for phonon transfer. As a result, the thermal conductivity (TC) of the obtained DANFC/Ag hybrid nanopapers containing only 1.9 vol % of Ag was 5.35 times higher than that of the pure NFC nanopapers along with a significantly TC enhancement per vol % Ag of 230.0%, which was supposed to benefit from the continuous heat transfer pathway constructed by the connection of AgNPs decorated on the cellulose nanofibers. The DANFC/Ag hybrid nanopapers possess potential applications as thermal management materials in the next-generation portable electronic devices.

16.
Int J Oncol ; 59(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34278448

RESUMO

Intrinsic or acquired resistance to temozolomide (TMZ) is a frequent occurrence in patients with glioblastoma (GBM). Accumulating evidence has indicated that the exosomal transfer of proteins and RNAs may confer TMZ resistance to recipient cells; however, the potential molecular mechanisms are not fully understood. Thus, the aim of the present study was to elucidate the possible role of exosomal microRNAs (miRNAs/miRs) in the acquired resistance to TMZ in GBM. A TMZ­resistant GBM cell line (A172R) was used, and exosomes derived from A172R cells were extracted. Exosomal miR­25­3p was identified as a miRNA associated with TMZ resistance. The potential functions of exosomal miR­25­3p were evaluated by reverse transcription­quantitative PCR, as well as cell viability, colony formation and soft agar assay, flow cytometry, western blot analysis, BrdU incorporation assay, tumor xenograft formation, luciferase reporter assay and RNA immunoprecipitation. It was found that A172R­derived exosomes promoted the proliferation and TMZ resistance of sensitive GBM cells. Moreover, miR­25­3p epxression was upregulated in the exosomes of A172R cells and in serum samples of patients with GBM treated with TMZ. The depletion of exosomal miR­25­3p partially abrogated the effects induced by the transfer of exosomes from A172R cells. By contrast, miR­25­3p overexpression facilitated the proliferation and TMZ resistance of sensitive GBM cells. F­box and WD repeat domain­containing­7 (FBXW7) was identified as a direct target of miR­25­3p. FBXW7 knockdown promoted the proliferation and TMZ resistance of GBM cells. Furthermore, the exosomal transfer of miR­25­3p promoted c­Myc and cyclin E expression by downregulating FBXW7. Our results provided a novel insight into exosomal microRNAs in acquired TMZ resistance of GBM cells. Besides, exosomal miR­25­3p might be a potential prognostic marker for GBM patients.

17.
J Nat Prod ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34279099

RESUMO

Two novel rearranged Diels-Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A-D (3-6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7 and 8) and two 2-arylbenzofurans (9 and 10). Morunigrines A (1) and B (2) are a novel class of Diels-Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone-stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6 was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1 and 2 is also proposed. Compounds 1 and 2 exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.8 ± 0.2 and 1.3 ± 0.3 µM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 µM).

18.
BMC Womens Health ; 21(1): 263, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210307

RESUMO

BACKGROUND: Endometriosis of the uterine body can be manifested as diffuse solid lesions or cystic lesions. The former is common, while the latter is rare, especially for cystic adenomyosis larger than 5 cm. CASE PRESENTATION: A 30-year-old woman was admitted for severe and worsening dysmenorrhea. Ultrasound examination revealed a rare well-circumscribed cystic lesion about 5.5 × 4 × 5.0 cm. CA-125 level was slightly elevated. She accepted laparoscopic surgery and the adenomyotic tissues were excised. The histopathology of the specimen demonstrated the endometrial glands in the walls of cysts and an area of extensive hemorrhage can be seen in the inner wall of cyst. The patient made a good recovery after surgery and her symptoms complete resoluted. CONCLUSIONS: This is a rare case of a cystic adenomyotic lesion that was treated by laparoscopic surgery.


Assuntos
Adenomiose , Cistos , Endometriose , Laparoscopia , Adenomiose/diagnóstico por imagem , Adenomiose/cirurgia , Adulto , Cistos/diagnóstico por imagem , Cistos/cirurgia , Dismenorreia/etiologia , Endometriose/diagnóstico por imagem , Endometriose/cirurgia , Feminino , Humanos
19.
J Am Chem Soc ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34270238

RESUMO

Constructing supramolecular cages with multiple subunits via weak intermolecular interactions is a long-standing challenge in chemistry. So far, π-stacked supramolecular cages still remain unexplored. Here, we report a series of π-stacked cage based hierarchical self-assemblies. The π-stacked cage (π-MX-cage) is assembled from 16 [MXL]+ ions (M = Mn2+, Co2+; X = Br-, SCN-, Cl-; and L = tris(2-benzimidazolylmethyl)amine) via 18 intermolecular π-stacking interactions. The tetrahedral cage, consisting of four [MXL]+ ions as the vertexes and six pairs of [MXL]+ ions as the edges, features 48 exterior N-H hydrogen bond donors for hydrogen bond formation with guest molecules. By variation of the M2+/X- pair, the π-MX-cage demonstrates unique versatility for incorporating a wide variety of species via different hydrogen-bonding modes during the assembly of hierarchical superstructures. In specific, the π-MnBr-cages encapsulate acetonitrile (CH3CN) or cis-1,3,5-cyclohexanetricarbonitrile (cis-HTN) molecules in the central voids, while a core-shell tetrahedral inorganic cluster [Mn(H2O)6]@([Mn(H2O)4]4[Br42-]6) (Mn@Mn4-cage) is captured within the interstitial regions between cages. The π-CoSCN-cages are capable of stabilizing reactive sulfur-containing species, such as S2O42-, S2O62-, and HSO3- ions, in the hierarchical superstructure. Finally, H2PO4- ions are incorporated between π-CoCl-cages, resulting in an inorganic mesoporous framework. These results provide insights into further exploring the chemistry and hierarchical assembly of supramolecular cages based on π-π stacking intermolecular interactions.

20.
Phys Chem Chem Phys ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34270659

RESUMO

The electrocatalytic hydrogen evolution reaction (HER) for water splitting is crucial for the sustainable production of clean hydrogen fuel, while the high cost of Pt catalysts impedes its commercialization. Herein, we have performed a systematic theoretical study on the electrocatalytic HER over single-atom catalysts (SACs) based on low-cost TiN. Specifically, the TiN(100) surface with a Ti or N vacancy has been considered as the support. 20 transition-metal (TM) atoms and 3 nonmetallic atoms are embedded into the Ti or N vacancy, accordingly denoted as M@Tiv or M@Nv. All the single atoms can be stabilized by the surface vacancies, controlled by the adjustable chemical potential. Interestingly, for TM-embedded TiN(100), the hydrogen binding is much stronger over M@Nv than M@Tiv, which can be attributed to the more localized d states of the TM atoms anchored by the N vacancies, indicating a strong coordination effect. Among 43 catalysts, 10 (Ni, Zn, Nb, Mo, Rh@Tiv, and Au, Pd, W, Mo, B@Nv) were predicted to have high HER catalytic activity with near-zero hydrogen adsorption free energy. For the further gaseous hydrogen evolution, Zn@Tiv can adopt both Tafel (with an energy barrier of 0.68 eV) and Heyrovsky mechanisms, while the others may prefer the Heyrovsky mechanism. This work provides a promising strategy to realize cost-efficient electrocatalysts for the HER, and highlights the important role of the local coordination environment for SACs.

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