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1.
PLoS One ; 16(10): e0246874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34624043

RESUMO

The aim of this study is to optimize the simulation result of the WOFOST model and explore the possibility of assimilating unmanned aerial vehicle (UAV) imagery into this model. Field images of wheat during its key growth stages are acquired with a UAV, and the corresponding leaf area index (LAI), biomass, and final yield are experimentally measured. LAI data is retrieved from the UAV imagery and assimilated into a localized WOFOST model using least squares optimization. Sensitive parameters, i.e., specific leaf area (SLATB0, SLATB0.5, SLATB2) and maximum CO2 assimilation rate (AMAXTB1, AMAXTB1.3) are adjusted to minimize the discrepancy between the LAI obtained from the model simulation and inversion of the UAV data. The results show that the assimilated model provides a better estimation of the growth and development of winter wheat in the study area. The R2, RMSE, and NRMSE of winter wheat LAI simulated with the assimilated WOFOST model are 0.8812, 0.49, and 23.5% respectively. The R2, RMSE, and NRMSE of the simulated yield are 0.9489, 327.06 kg·hm-2, and 6.5%. The accuracy in model simulation of winter wheat growth is improved, which demonstrates the feasibility of integrating UAV data into crop models.

2.
Am J Transl Res ; 13(9): 10593-10598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650731

RESUMO

OBJECTIVE: To investigate the application and clinical efficacy of "Trinity" nursing mode in bronchial asthma health management. METHODS: A total of 100 patients with bronchial asthma admitted to our hospital from June 2017 to June 2020 were divided into a reference group and a research group according to the order of admission (50 cases in each group). The reference group received conventional nursing, while the research group received "Trinity" nursing. The control of asthma, health literacy, hospitalization, treatment compliance and disease recurrence rate were compared between the two groups. RESULTS: The asthma control test (ACT) score of the research group was higher than that of the reference group; the health literacy score of the research group was higher than that of the reference group; the hospitalization time and treatment cost of the research group were less compared to the reference group. After 1 month of treatment, there was no significant difference between the two groups, and the compliance of the research group was significantly higher than that of the latter after 3 months and 6 months of treatment. The disease recurrence of the research group was significantly lower compared to the reference group 1 month, 3 months, and 6 months after treatment, respectively (P<0.05). CONCLUSION: "Trinity" nursing mode has a positive clinical effect in the health management of bronchial asthma, which can promote respiratory function and health literacy of patients, help patients save hospitalization expenses, improve treatment compliance and control the recurrence of asthma diseases. Therefore, it is worthy of promotion.

3.
Adv Mater ; : e2104658, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34642998

RESUMO

2D layered chalcogenide semiconductors have been proposed as a promising class of materials for low-dimensional electronic, optoelectronic, and spintronic devices. Here, all-2D van der Waals vertical spin-valve devices, that combine the 2D layered semiconductor InSe as a spacer with the 2D layered ferromagnetic metal Fe3 GeTe2 as spin injection and detection electrodes, are reported. Two distinct transport behaviors are observed: tunneling and metallic, which are assigned to the formation of a pinhole-free tunnel barrier at the Fe3 GeTe2 /InSe interface and pinholes in the InSe spacer layer, respectively. For the tunneling device, a large magnetoresistance (MR) of 41% is obtained under an applied bias current of 0.1 µA at 10 K, which is about three times larger than that of the metallic device. Moreover, the tunneling device exhibits a lower operating bias current but a more sensitive bias current dependence than the metallic device. The MR and spin polarization of both the metallic and tunneling devices decrease with increasing temperature, which can be fitted well by Bloch's law. These findings reveal the critical role of pinholes in the MR of all-2D van der Waals ferromagnet/semiconductor heterojunction devices.

4.
BMC Genomics ; 22(1): 750, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663228

RESUMO

BACKGROUND: Chloroplast transfer RNAs (tRNAs) can participate in various vital processes. Gymnosperms have important ecological and economic value, and they are the dominant species in forest ecosystems in the Northern Hemisphere. However, the evolution and structural changes in chloroplast tRNAs in gymnosperms remain largely unclear. RESULTS: In this study, we determined the nucleotide evolution, phylogenetic relationships, and structural variations in 1779 chloroplast tRNAs in gymnosperms. The numbers and types of tRNA genes present in the chloroplast genomes of different gymnosperms did not differ greatly, where the average number of tRNAs was 33 and the frequencies of occurrence for various types of tRNAs were generally consistent. Nearly half of the anticodons were absent. Molecular sequence variation analysis identified the conserved secondary structures of tRNAs. About a quarter of the tRNA genes were found to contain precoded 3' CCA tails. A few tRNAs have undergone novel structural changes that are closely related to their minimum free energy, and these structural changes affect the stability of the tRNAs. Phylogenetic analysis showed that tRNAs have evolved from multiple common ancestors. The transition rate was higher than the transversion rate in gymnosperm chloroplast tRNAs. More loss events than duplication events have occurred in gymnosperm chloroplast tRNAs during their evolutionary process. CONCLUSIONS: These findings provide novel insights into the molecular evolution and biological characteristics of chloroplast tRNAs in gymnosperms.


Assuntos
Cycadopsida , Ecossistema , Cloroplastos/genética , Cycadopsida/genética , Filogenia , RNA de Transferência/genética
5.
Phys Rev Lett ; 127(11): 116402, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34558920

RESUMO

We propose a general and tunable platform to realize high-density arrays of quantum spin-valley Hall kink (QSVHK) states with spin-valley-momentum locking based on a two-dimensional hexagonal topological insulator. Through the analysis of Berry curvature and topological charge, the QSVHK states are found to be topologically protected by the valley-inversion and time-reversal symmetries. Remarkably, the conductance of QSVHK states remains quantized against both nonmagnetic short- and long-range and magnetic long-range disorder, verified by the Green-function calculations. Based on first-principles results and our fabricated samples, we show that QSVHK states, protected with a gap up to 287 meV, can be realized in bismuthene by alloy engineering, surface functionalization, or electric field, supporting nonvolatile applications of spin-valley filters, valves, and waveguides even at room temperature.

6.
Biochem Biophys Res Commun ; 577: 130-138, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34517210

RESUMO

Gliomas are the major type of primary brain tumors. Accumulating research has demonstrated that tubulin is connected with the development and malignant progression of tumors. TUBA1C is a subtype of α-tubulin and is linked to prognosis in multiple cancers. In this study, the prognosis-related gene TUBA1C in glioma was identified and analyzed by bioinformatic approaches such as Kaplan-Meier (KM) survival time analysis, univariate and multivariate Cox analysis, receiver operating characteristic (ROC) analysis and functional enrichment analysis. Based on the above analyses, we found that glioma tissues had significantly higher expression of TUBA1C than normal brain tissues, and high expression of TUBA1C has worse prognosis in glioma. Gene set enrichment analysis (GSEA) revealed the signaling pathways related to the cell cycle. Furthermore, knockdown of TUBA1C also inhibited proliferation and migration and caused apoptosis and G2/M phase arrest in glioma cells. This study demonstrated that high TUBA1C expression correlated with poor outcomes in glioma patients and that knocking down TUBA1C suppressed glioma cell proliferation via cell cycle arrest. In addition, TUBA1C might be a therapeutic biomarker for gliomas.

7.
Clin Immunol ; 232: 108852, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520860

RESUMO

BACKGROUND: The majority of the coronavirus disease 2019 (COVID-19) non-survivors meet the criteria for disseminated intravascular coagulation (DIC). Although timely monitoring of clotting hemorrhagic development during the natural course of COVID-19 is critical for understanding pathogenesis, diagnosis, and treatment of the disease, however, limited data are available on the dynamic processes of inflammation/coagulopathy/fibrinolysis (ICF). METHODS: We monitored the dynamic progression of ICF in patients with moderate COVID-19. Out of 694 COVID-19 inpatients from 10 hospitals in Wenzhou, China, we selected 293 adult patients without comorbidities. These patients were divided into different daily cohorts according to the COVID-19 onset-time. Furthermore, data of 223 COVID-19 patients with comorbidities and 22 critical cases were analyzed. Retrospective data were extracted from electronic medical records. RESULTS: The virus-induced damages to pre-hospitalization patients triggered two ICF fluctuations during the 14-day course of the disease. C-reactive protein (CRP), fibrinogen, and D-dimer levels increased and peaked at day 5 (D) 5 and D9 during the 1st and 2nd fluctuations, respectively. The ICF activities were higher during the 2nd fluctuation. Although 12-day medication returned high CRP concentrations to normal and blocked fibrinogen increase, the D-dimer levels remained high on days 17 ±â€¯2 and 23 ±â€¯2 days of the COVID-19 course. Notably, although the oxygenation index, prothrombin time and activated partial thromboplastin time were within the normal range in critical COVID-19 patients at administration, 86% of these patients had a D-dimer level > 500 µg/L. CONCLUSION: COVID-19 is linked with chronic DIC, which could be responsible for the progression of the disease. Understanding and monitoring ICF progression during COVID-19 can help clinicians in identifying the stage of the disease quickly and accurately and administering suitable treatment.

8.
J Fam Psychol ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472935

RESUMO

Family lives have been changed dramatically due to the stay-at-home orders implemented during the coronavirus disease 2019 (COVID-19) outbreak. A variety of factors serve to increase the risk for children and adolescents in developing mental health issues during the prolonged stay-at-home period. The primary aim of this study was to examine a complex conceptual model linking daily routines, parent-child conflict, and indices of psychological maladjustment during the COVID-19 pandemic in a large sample of Chinese children and adolescents. Participants were N = 1,594 children and adolescents (50.6% girls; Mage = 13.13, SDage = 1.54) and their mothers, from Zhengzhou in Mainland China. Multisource assessments include youth self-reports of loneliness, depressive symptoms, and perceived conflict with parents during the stay-at-home period, as well as maternal reports of their child's daily routines during this time. Among the results, parent-child conflict mediated the relations between daily routines and indices of psychological maladjustment, such that a lack of routine predicted greater parent-child conflict, which in turn was associated with higher levels of loneliness and symptoms of depression. Further, results from multiple group analyses revealed that associations between daily routines and maladjustment were stronger among boys than girls-as well as stronger among primary school children than middle school adolescents. Findings highlighted the importance of maintaining regular routines for children's and adolescents' mental health during the COVID-19 pandemic. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

9.
Front Immunol ; 12: 718073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504496

RESUMO

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder in the elderly. Systemic and topical use of glucocorticoids and immunosuppressants has been shown to be effective in most patients. However, refractory BP patients are challenged to clinicians with severe clinical symptoms, resistance to treatment, and high relapse rate. How to predict and assess the refractory and severity of bullous pemphigoid is the key issue in clinical practice, and the urgent need for precision medicine in refractory patients is driving the search for biomarkers and biologics. Recently, some biomarkers, such as the level of specific autoantibodies and released cytokines, have been proposed as the potential parameters to reflect the disease severity and predict the treatment response and relapse of refractory BP. Moreover, new biologics targeting pathogenic antibodies, complement, Th2 axis, eosinophils, and Th17 axis have shown potent efficacy on refractory BP. Here, we review the literature and give an overview of emerging biomarkers and therapeutic strategies for refractory bullous pemphigoid to improve the prognosis of the patient.

10.
Biomed Mater ; 16(6)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34450597

RESUMO

The modulation of inflammation in tissue microenvironment takes an important role in cartilage repair and regeneration. In this study, a novel hybrid scaffold was designed and fabricated by filling a reactive oxygen species (ROS)-scavenging hydrogel (RS Gel) into a radially oriented poly(lactide-co-glycolide) (PLGA) scaffold. The radially oriented PLGA scaffolds were fabricated through a temperature gradient-guided phase separation and freeze-drying method. The RS Gel was formed by crosslinking the mixture of ROS-responsive hyperbranched polymers and biocompatible methacrylated hyaluronic acid (HA-MA). The hybrid scaffolds exhibited a proper compressive modulus, good ROS-scavenging capability, and cell compatibility.In vivotests showed that the hybrid scaffolds significantly regulated inflammation and promoted regeneration of hyaline cartilage after they were implanted into full-thickness cartilage defects in rabbits for 12 w. In comparison with the PLGA scaffolds, the neo-cartilage in the hybrid scaffolds group possessed more deposition of glycosaminoglycans and collagen type II, and were well integrated with the surrounding tissue.

11.
Aging (Albany NY) ; 13(16): 20302-20318, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425560

RESUMO

Cancer development and progression can be regulated by the levels of endogenous factors. Gastric cancer is an aggressive disease state with poor patient prognosis, needing the development of new diagnostics and therapeutic strategies. We investigated the close association between follistatin-like 3 (FSTL3) and different cancers, and focused on its role in gastric cancer cell function. Using cancer bioinformatics, we found that FSTL3 expression is elevated in a large majority of the 33 cancers we analyzed in publicly available cancer databases. Elevated levels of FSTL3 is associated with poor patient prognosis in gastric cancer. In a comparison of normal gastric epithelial cells and gastric cancer cell lines, FSTL3 expression was consistently elevated in gastric cancer cells. Overexpression of FSTL3 promoted gastric cancer cell viability, proliferation and migration. Conversely, FSTL3 knockdown inhibits these cellular processes. Using bioinformatics, we found that the FSTL3 mRNA has a potential binding site in the 3'-UTR for a small microRNA, miR-486-5p. Further bioinformatics revealed significant negative correlation between FSTL3 and miR-486-5p levels. Using luciferase reporter constructs, we provide evidence that the 3'UTR from the FSTL3 mRNA can confer downregulation in the presence of miR-486-5p. These studies lead us to conclude that FSTL3 has oncogenic properties and increased expression of this gene product promotes gastric cancer development and progression.

12.
Sci Rep ; 11(1): 16268, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381120

RESUMO

Volume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα+ cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα+ cell density was also documented. Loss of PDGFRα+ cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα+ cells is causative in the development of DO after SCI.

13.
J Ethnopharmacol ; 281: 114575, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34461190

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Embelia laeta (L.) Mez., which is called Suanjifeng in Chinese ethnic Yao medicine, is traditionally for inflammation-related diseases, such as oral ulcer, sore throat, enteritis, and rheumatoid arthritis. However, the biological properties and the underlying mechanisms of Embelia laeta still need further studies. AIM OF THIS STUDY: The present study aims to investigate the anti-inflammatory effect and its underlying mechanisms of Embelia laeta. MATERIALS AND METHODS: In this study, except acute toxicity experiments, Kunming (KM) mice of either sex were enrolled to establish inflammatory model induced by xylene, acetic acid and carrageenan, respectively. Mice were randomly divided into different groups and pretreated by oral gavage with different doses of Embelia laeta aqueous extract (ELAE) (2.5, 5, 10 g/kg) and 10 mg/kg of Indo for 7 days. Ear edema, vascular permeability, abdominal writhing, and paw edema degree were detected in related experiments. Moreover, in the carrageenan-induced paw edema mice model, histological changes were detected by H&E staining. MDA, MPO and NO were detected by assay kit. Proinflammatory cytokines of IFN-γ, TNF-α, IL-1ß, IL-6 and PGE2 were detected by ELISA. Additionally, COX-2, iNOS and NF-κB pathway-related proteins were detected by Western blotting. RESULTS: Results showed that the ELAE evoked an obvious dose-dependent inhibition of ear edema induced by xylene, paw edema induced by carrageenan, as well as suppressing the increase of vascular permeability and writhing times elicited by acetic acid. Histopathological analysis indicated that ELAE could significantly decrease the cellular infiltration in paw tissue. ELAE showed antioxidant property through markedly decrease the MDA level and MPO activity in edema paw. In addition, ELAE decreased the proinflammatory cytokines IFN-γ, TNF-α, IL-1ß, IL-6, PGE2 and NO that induced by carrageenan. Western blotting results also showed that ELAE could obviously downregulate the COX-2 and iNOS expression. Further analysis revealed that ELAE also inhibited NF-κB from the cytoplasm to the nucleus and stabilize the conversion of IκBα. CONCLUSION: ELAE had powerful anti-inflammatory property, which might be had a close relationship with mediating proinflammatory cytokines production, decreasing the COX-2 and iNOS expression, and inhibiting the activation of NF-κB signaling pathway.

14.
Mol Med Rep ; 24(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34368871

RESUMO

N­methyl D­aspartate receptors (NMDARs) are closely associated with the development, growth and metastasis of cancer. Glutamate receptor, ionotropic, N­methyl D­aspartate­associated protein 1 (GRINA) is a member of the of the NMDAR family, and its aberrant expression is associated with gastric cancer. However, the role of GRINA in colorectal cancer (CRC) is not completely understood. In the present study, expression profiles of GRINA in several CRC databases were obtained and further verified using clinical CRC samples. The effects of GRINA overexpression on CRC progression both in vivo and in vitro were assessed. Briefly, cell proliferation was detected using MTT assay, and cell migration and invasion ability were evaluated by wound healing and Transwell assay. In addition, the molecular mechanism underlying the upregulated expression of GRINA in CRC was investigated. The regulatory association between GRINA and miR­296­3p was detected by luciferase assay, reverse transcription­quantitative PCR and western blotting. The results demonstrated that GRINA expression levels were significantly increased in tumor samples compared with those in healthy samples, and upregulated expression of GRINA was associated with a less favorable prognostic outcome in patients with CRC. GRINA overexpression significantly increased CRC cell proliferation, invasion and migration. Additionally, it was determined that GRINA was post­transcriptionally regulated by microRNA (miR)­296­3p. Together, the results of the present study suggested the potential importance of the miR­296­3p/GRINA axis and highlighted potential novel targets for the management of CRC.

15.
Front Cell Dev Biol ; 9: 701247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422822

RESUMO

Objectives: HIF2α is of vital importance in the regulation of endothelial dysfunction, cell proliferation, migration, and pulmonary vascular remodeling in pulmonary hypertension. Our previous studies demonstrated that conditional and inducible deletion of HIF2α in mouse lung endothelial cells, dramatically protected the mice against vascular remodeling and the development of pulmonary arterial hypertension (PAH). Here, we provide a novel transcriptome insight into the impact of HIF2α in PAH pathogenesis and the potential to use HIF2α-mediated gene sets to differentiate PAH human subjects. Methods: Using transcriptome data, we first tapped the value of the difference in gene expression profile between wild type (WT) and Hif2a knockdown (KD) cell lines. We considered the deregulated genes between WT and Hif2a-KD cells as HIF2α influenced genes. By examining the lung tissue transcriptome data set with nine controls and eight PAH patients, we evaluated the HIF2α regulatory network in PAH pathogenesis to further determine the identification ability of HIF2α-mediated gene sets in human PAH subjects. On the other hand, using peripheral blood mononuclear cells (PBMCs) transcriptome data from PAH patients and healthy controls, we further validated the potential of the HIF2α-mediated PBMC gene sets as a possible diagnostic tool for PAH. To verify the ability of HIF2α-mediated gene sets for the identification of PAH, endothelial cell-specific Phd2 knockout mice with spontaneous pulmonary hypertension were used for reverse validation experiments. Results: 19 identified GO biological process terms were significantly correlated with the genes down-regulated in Hif2a-KD cells, all of which are strongly related to the PAH pathogenesis. We further assessed the discriminative power of these HIF2α-mediated gene sets in PAH human subjects. We found that the expression profile of the HIF2α-mediated gene sets in lung tissues and PBMCs were differentiated both between controls and PAH patients. Further, a significant positive correlation was observed between hypoxia and Phd2 deficiency mediated gene set expression profiles. As expected, 7 of the 19 significantly down-regulated GO terms in Hif2a-KD cells were found to overlap with the up-regulated GO gene sets in Phd2 EC-/- mice compared to WT controls, suggesting opposing effects of HIF2α and PHD2 on PAH pathogenesis. Conclusion: HIF2α-mediated gene sets may be used to differentiate pulmonary arterial hypertension.

17.
Evol Bioinform Online ; 17: 11769343211035140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366661

RESUMO

The RNA G-quadruplex (rG4) is a kind of non-canonical high-order secondary structure with important biological functions and is enriched in untranslated regions (UTRs) of protein-coding genes. However, how rG4 structures evolve is largely unknown. Here, we systematically investigated the evolution of RNA sequences around UTR rG4 structures in 5 eukaryotic organisms. We found universal selection on UTR sequences, which facilitated rG4 formation in all the organisms that we analyzed. While G-rich sequences were preferred in the rG4 structural region, C-rich sequences were selectively not preferred. The selective pressure acting on rG4 structures in the UTRs of genes with higher G content was significantly smaller. Furthermore, we found that rG4 structures experienced smaller evolutionary selection near the translation initiation region in the 5' UTR, near the polyadenylation signals in the 3' UTR, and in regions flanking the miRNA targets in the 3' UTR. These results suggest universal selection for rG4 formation in the UTRs of eukaryotic genomes and the selection may be related to the biological functions of rG4s.

18.
Nanomicro Lett ; 13(1): 172, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383132

RESUMO

Thanks to the excellent optoelectronic properties, lead halide perovskites (LHPs) have been widely employed in high-performance optoelectronic devices such as solar cells and light-emitting diodes. However, overcoming their poor stability against water has been one of the biggest challenges for most applications. Herein, we report a novel hot-injection method in a Pb-poor environment combined with a well-designed purification process to synthesize water-dispersible CsPbBr3 nanocrystals (NCs). The as-prepared NCs sustain their superior photoluminescence (91% quantum yield in water) for more than 200 days in an aqueous environment, which is attributed to a passivation effect induced by excess CsBr salts. Thanks to the ultra-stability of these LHP NCs, for the first time, we report a new application of LHP NCs, in which they are applied to electrocatalysis of CO2 reduction reaction. Noticeably, they show significant electrocatalytic activity (faradaic yield: 32% for CH4, 40% for CO) and operation stability (> 350 h).

19.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34301815

RESUMO

BACKGROUND: Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers. METHODS: Balb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent 18F-FDG and 89Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope. RESULTS: Preclinical studies showed that 89Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of 89Zr-CTB006 with a mean maximum standardized uptake value (SUVmax) of 6.63±3.29 (range 1.8-13.8). Tumor tissue was obtained from 18 patients, and 89Zr-CTB006 uptake in patients with RNAscope scores of 3-4 was significantly higher than that in patients with scores of 0-2. An SUVmax of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively. CONCLUSIONS: 89Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression.

20.
Int J Biol Sci ; 17(9): 2278-2293, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239355

RESUMO

Effectively targeting cancer stem cells to treat cancer has great therapeutic prospects. However, the effect of microRNA miR-17/MKL-1 on gastric cancer stem cells has not been studied yet. This study preliminarily explored the mechanism of miR-17/MKL-1 in gastric cancer stem cells. Many previous reports have indicated that microRNA and EMT regulated cancer stem cell characteristics, and miR-17 and MKL-1 were involved as a critical gene in migration and invasion in the EMT pathway. Through RT-PCR, Western Blot, flow cytometry, immunofluorescence, sphere formation xenograft tumor assays and drug resistance, the role of miR-17-5p and MKL-1 on promoting stem cell-like properties of gastric cancer were verified in vivo and vitro. Next, MKL-1 targets CD44, EpCAM, and miR -17-5p promoter verified by luciferase assay and ChIP. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. It is found that MKL-1 promotes expression by targeting miR-17, CD44 and EpCAM promoters. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. These findings reveal new regulatory signaling pathways for gastric cancer stem cells, thus it give new insights on potential early diagnosis and/or molecular therapy for gastric cancer.

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