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  • 1
    Online Resource
    Online Resource
    The Synergistic Effect of Biochar-Combined Activated Phosphate Rock Treatments in Typical Vegetables in Tropical Sandy Soil: Results from Nutrition Supply and the Immobilization of Toxic Metals
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 11 ( 2022-05-25), p. 6431-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 11 ( 2022-05-25), p. 6431-
    Abstract: Sandy soils in tropical areas are more vulnerable to potential toxic elements as a result of their low nutrition. The composite addition of biochar and phosphate material is considered a promising method of immobilizing toxic metals in sandy soils, but the synergistic effects of this process still need to be further explored, especially in typical tropical vegetables. In this study, a pot experiment was conducted to evaluate the agronomic and toxic metal-immobilization effects of single amendments (phosphate rock, activated phosphate rock, and biochar) and combined amendments, including biochar mixed with phosphate rock (BCPR) and biochar mixed with activated phosphate rock (BCAPR), on vegetables grown in tropical sandy soil. Among these amendments, the composite amendment BCAPR was the most effective for increasing Ca, Mg, and P uptake based on water spinach (Ipomoea aquatica L.) and pepper (Capsicum annuum L.), showing increased ratios of 22.5%, 146.0%, and 136.0%, respectively. The SEM-EDS and FTIR analysis verified that the activation process induced by humic acid resulted in the complexation and chelation of the elements P, Ca, and Mg into bioavailable forms. Furthermore, the retention of available nutrition elements was enhanced due to the strong adsorption capacity of the biochar. In terms of cadmium (Cd) and lead (Pb) passivation, the formation of insoluble mineral precipitates reduced the mobility of these metals within the BCAPR treatments, with the maximum level of extractable Cd (86.6%) and Pb (39.2%) reduction being observed in the tropical sandy soil. These results explore the use of sustainable novel cost-effective and highly efficient bi-functional mineral-based soil amendments for metal passivation and plant protection.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19116431
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 2
    Online Resource
    Online Resource
    Concurrent Chemoradiotherapy-Driven Cell Plasticity by miR-200 Family Implicates the Therapeutic Response of Esophageal Squamous Cell Carcinoma
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 8 ( 2022-04-14), p. 4367-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 8 ( 2022-04-14), p. 4367-
    Abstract: Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy with an increasing incidence worldwide. Over the past decade, concurrent chemoradiotherapy (CCRT) with or without surgery is an emerging therapeutic approach for locally advanced ESCC. Unfortunately, many patients exhibit poor response or develop acquired resistance to CCRT. Once resistance occurs, the overall survival rate drops down rapidly and without proper further treatment options, poses a critical clinical challenge for ESCC therapy. Here, we utilized lab-created CCRT-resistant cells as a preclinical study model to investigate the association of chemoradioresistantresistance with miRNA-mediated cell plasticity alteration, and to determine whether reversing EMT status can re-sensitize refractory cancer cells to CCRT response. During the CCRT treatment course, refractory cancer cells adopted the conversion of epithelial to mesenchymal phenotype; additionally, miR-200 family members were found significantly down-regulated in CCRT resistance cells by miRNA microarray screening. Down-regulated miR-200 family in CCRT resistance cells suppressed E-cadherin expression through snail and slug, and accompany with an increase in N-cadherin. Rescuing expressions of miR-200 family members in CCRT resistance cells, particularly in miR-200b and miR-200c, could convert cells to epithelial phenotype by increasing E-cadherin expression and sensitize cells to CCRT treatment. Conversely, the suppression of miR-200b and miR-200c in ESCC cells attenuated E-cadherin, and that converted cells to mesenchymal type by elevating N-cadherin expression, and impaired cell sensitivity to CCRT treatment. Moreover, the results of ESCC specimens staining established the clinical relevance that higher N-cadherin expression levels associate with the poor CCRT response outcome in ESCC patients. Conclusively, miR-200b and miR-200c can modulate the conversion of epithelial–mesenchymal phenotype in ESCC, and thereby altering the response of cells to CCRT treatment. Targeting epithelial–mesenchymal conversion in acquired CCRT resistance may be a potential therapeutic option for ESCC patients.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23084367
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Salvage Boron Neutron Capture Therapy for Malignant Brain Tumor Patients in Compliance with Emergency and Compassionate Use: Evaluation of 34 Cases in Taiwan
    MDPI AG ; 2021
    In:  Biology Vol. 10, No. 4 ( 2021-04-15), p. 334-
    Details
    In: Biology, MDPI AG, Vol. 10, No. 4 ( 2021-04-15), p. 334-
    Abstract: Although boron neutron capture therapy (BNCT) is a promising treatment option for malignant brain tumors, the optimal BNCT parameters for patients with immediately life-threatening, end-stage brain tumors remain unclear. We performed BNCT on 34 patients with life-threatening, end-stage brain tumors and analyzed the relationship between survival outcomes and BNCT parameters. Before BNCT, MRI and 18F-BPA-PET analyses were conducted to identify the tumor location/distribution and the tumor-to-normal tissue uptake ratio (T/N ratio) of 18F-BPA. No severe adverse events were observed (grade ≥ 3). The objective response rate and disease control rate were 50.0% and 85.3%, respectively. The mean overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) times were 7.25, 7.80, and 4.18 months, respectively. Remarkably, the mean OS, CSS, and RFS of patients who achieved a complete response were 17.66, 22.5, and 7.50 months, respectively. Kaplan–Meier analysis identified the optimal BNCT parameters and tumor characteristics of these patients, including a T/N ratio ≥ 4, tumor volume 〈 20 mL, mean tumor dose ≥ 25 Gy-E, MIB-1 ≤ 40, and a lower recursive partitioning analysis (RPA) class. In conclusion, for malignant brain tumor patients who have exhausted all available treatment options and who are in an immediately life-threatening condition, BNCT may be considered as a therapeutic approach to prolong survival.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology10040334
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661517-4
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  • 4
    Online Resource
    Online Resource
    β-Delayed γ Emissions of 26P and Its Mirror Asymmetry
    MDPI AG ; 2021
    In:  Symmetry Vol. 13, No. 12 ( 2021-11-30), p. 2278-
    Details
    In: Symmetry, MDPI AG, Vol. 13, No. 12 ( 2021-11-30), p. 2278-
    Abstract: The study of the origin of asymmetries in mirror β decay is extremely important to understand the fundamental nuclear force and the nuclear structure. The experiment was performed at the National Laboratory of Heavy Ion Research Facility in Lanzhou (HIRFL) to measure the β-delayed γ rays of 26P by silicon array and Clover-type high-purity Germanium (HPGe) detectors. Combining with results from the β decay of 26P and its mirror nucleus 26Na, the mirror asymmetry parameter δ ( ≡ft+/ft−− 1) was determined to be 46(13)% for the transition feeding the first excited state in the daughter nucleus. Our independent results support the conclusion that the large mirror asymmetry is close to the proton halo structure in 26P.
    Type of Medium: Online Resource
    ISSN: 2073-8994
    URL: Article
    DOI: 10.3390/sym13122278
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518382-5
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  • 5
    Online Resource
    Online Resource
    NDAT Targets PI3K-Mediated PD-L1 Upregulation to Reduce Proliferation in Gefitinib-Resistant Colorectal Cancer
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 8 ( 2020-08-03), p. 1830-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 8 ( 2020-08-03), p. 1830-
    Abstract: The property of drug-resistance may attenuate clinical therapy in cancer cells, such as chemoresistance to gefitinib in colon cancer cells. In previous studies, overexpression of PD-L1 causes proliferation and metastasis in cancer cells; therefore, the PD-L1 pathway allows tumor cells to exert an adaptive resistance mechanism in vivo. Nano-diamino-tetrac (NDAT) has been shown to enhance the anti-proliferative effect induced by first-line chemotherapy in various types of cancer, including colorectal cancer (CRC). In this work, we attempted to explore whether NDAT could enhance the anti-proliferative effect of gefitinib in CRC and clarified the mechanism of their interaction. The MTT assay was utilized to detect a reduction in cell proliferation in four primary culture tumor cells treated with gefitinib or NDAT. The gene expression of PD-L1 and other tumor growth-related molecules were quantified by quantitative polymerase chain reaction (qPCR). Furthermore, the identification of PI3K and PD-L1 in treated CRC cells were detected by western blotting analysis. PD-L1 presentation in HCT116 xenograft tumors was characterized by specialized immunohistochemistry (IHC) and the hematoxylin and eosin stain (H & E stain). The correlations between the change in PD-L1 expression and tumorigenic characteristics were also analyzed. (3) The PD-L1 was highly expressed in Colo_160224 rather than in the other three primary CRC cells and HCT-116 cells. Moreover, the PD-L1 expression was decreased by gefitinib (1 µM and 10 µM) in two cells (Colo_150624 and 160426), but 10 µM gefitinib stimulated PD-L1 expression in gefitinib-resistant primary CRC Colo_160224 cells. Inactivated PI3K reduced PD-L1 expression and proliferation in CRC Colo_160224 cells. Gefitinib didn’t inhibit PD-L1 expression and PI3K activation in gefitinib-resistant Colo_160224 cells. However, NDAT inhibited PI3K activation as well as PD-L1 accumulation in gefitinib-resistant Colo_160224 cells. The combined treatment of NDAT and gefitinib inhibited pPI3K and PD-L1 expression and cell proliferation. Additionally, NDAT reduced PD-L1 accumulation and tumor growth in the HCT116 (K-RAS mutant) xenograft experiment. (4) Gefitinib might suppress PD-L1 expression but did not inhibit proliferation through PI3K in gefitinib-resistant primary CRC cells. However, NDAT not only down-regulated PD-L1 expression via blocking PI3K activation but also inhibited cell proliferation in gefitinib-resistant CRCs.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9081830
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 6
    Online Resource
    Online Resource
    Polymorphism Detection of GDF9 Gene and Its Association with Litter Size in Luzhong Mutton Sheep (Ovis aries)
    MDPI AG ; 2021
    In:  Animals Vol. 11, No. 2 ( 2021-02-22), p. 571-
    Details
    In: Animals, MDPI AG, Vol. 11, No. 2 ( 2021-02-22), p. 571-
    Abstract: Litter size is one of the most important economic traits in sheep. GDF9 and BMPR1B are major genes affecting the litter size of sheep. In this study, the whole coding region of GDF9 was sequenced and all the SNPs (single nucleotide polymorphisms) were determined in Luzhong mutton ewes. The FecB mutation was genotyped using the Sequenom MassARRAY®SNP assay technology. Then, the association analyses between polymorphic loci of GDF9 gene, FecB, and litter size were performed using a general linear model procedure. The results showed that eight SNPs were detected in GDF9 of Luzhong mutton sheep, including one novel mutation (g.41769606 T 〉 G). The g.41768501A 〉 G, g.41768485 G 〉 A in GDF9 and FecB were significantly associated with litter size in Luzhong mutton ewes. The g.41768485 G 〉 A is a missense mutation in the mature GDF9 protein region and is predicted to affect the tertiary structure of the protein. The results preliminarily demonstrated that GDF9 was a major gene affecting the fecundity of Luzhong mutton sheep and the two loci g.41768501A 〉 G and g.41768485 G 〉 A may be potential genetic markers for improving litter size.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani11020571
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 7
    Online Resource
    Online Resource
    Chemokine Receptors CCR6 and PD1 Blocking scFv E27 Enhances Anti-EGFR CAR-T Therapeutic Efficacy in a Preclinical Model of Human Non-Small Cell Lung Carcinoma
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 6 ( 2023-03-12), p. 5424-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 6 ( 2023-03-12), p. 5424-
    Abstract: Chimeric antigen receptor (CAR)-T cells, a therapeutic agent for solid tumors, are not completely effective due to a lack of infiltration of T cells into the tumor site and immunity caused by Programmed Death Receptor 1(PD1). Here, an epidermal growth factor receptor (EGFR) CAR-T cell was engineered to express the chemokine receptor CCR6 and secrete PD1 blocking Single-chain antibody fragment (scFv) E27 to enhance their anti-tumor effects. The findings showed that CCR6 enhanced the migration of EGFR CAR-E27-CCR6 T cells in vitro by the Transwell migration assay. When incubated with tumor cells, EGFR CAR-E27-CCR6 T cells specifically exerted potent cytotoxicity and produced high levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interferon-γ (IFN-γ). A non-small cell lung carcinoma (NSCLC) cell line-derived xenograft model was constructed by implanting modified A549 cell lines into immunodeficient NOD.PrkdcscidIl2rgem1/Smoc (NSG) mice. In comparison with traditional EGFR CAR-T cells, live imaging indicated that EGFR CAR-E27-CCR6 T cells displayed superior anti-tumor function. In addition, the histopathological examination of mouse organs showed no obvious organic damage. Our findings confirmed that PD1 blocking and CCR6 can enhance the anti-tumor function of EGFR CAR-T cells in an NSCLC xenograft model, providing an effective treatment strategy to improve the efficacy of CAR-T in NSCLC.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24065424
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Association of Body Mass Index with Long-Term All-Cause Mortality in Patients Who Had Undergone a Vertebroplasty for a Vertebral Compression Fracture
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 21 ( 2022-11-02), p. 6519-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 21 ( 2022-11-02), p. 6519-
    Abstract: We aimed to investigate the association between preoperative body mass index (BMI) and postoperative long-term mortality in patients who underwent a vertebroplasty. We retrospectively enrolled patients with a vertebral compression fracture who underwent a vertebroplasty between May 2013 and June 2020 in a medical center in Taiwan. The survival status of the study sample was confirmed by the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of being overweight/obese (≥25 kg/m2 vs. 〈 25 kg/m2) and BMI (as a continuous variable) on all-cause mortality after adjusting for age, sex, history of smoking, diabetes, hypertension, chronic kidney disease, and osteoporosis. A total of 164 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.6%, mean BMI 24.0 ± 4.1 kg/m2) after a median follow-up of 785 days. Compared with a BMI 〈 25 kg/m2, a BMI ≥ 25 kg/m2 was associated with a significantly lower risk of all-cause mortality (HR 0.297, 95% CI 0.101 to 0.878, p = 0.028). These findings were consistent when BMI was examined as a continuous variable (HR 0.874, 95% CI 0.773 to 0.988, p = 0.031). A low BMI ( 〈 22 kg/m2) should be considered as a risk factor for postoperative long-term mortality in this ageing population.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11216519
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 9
    Online Resource
    Online Resource
    Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells
    MDPI AG ; 2020
    In:  Marine Drugs Vol. 18, No. 7 ( 2020-07-02), p. 348-
    Details
    In: Marine Drugs, MDPI AG, Vol. 18, No. 7 ( 2020-07-02), p. 348-
    Abstract: Background: Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit p53 expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, activates p53 and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells. Methods: We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3’,5,5’-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells. Results: Heteronemin inhibited not only expression of proliferative genes and Homo Sapiens Thrombospondin 1 (THBS-1) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased TGF-β1 expression in SCC-25 cells. Tetrac suppressed expression of THBS-1 but not p53 expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent. Conclusions: Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited THBS-1 expression. Moreover, tetrac suppressed TGF-β expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells.
    Type of Medium: Online Resource
    ISSN: 1660-3397
    URL: Article
    DOI: 10.3390/md18070348
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175190-0
    SSG: 15,3
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  • 10
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    Online Resource
    A Special Phenotype of Aconidial Aspergillus niger SH2 and Its Mechanism of Formation via CRISPRi
    MDPI AG ; 2022
    In:  Journal of Fungi Vol. 8, No. 7 ( 2022-06-28), p. 679-
    Details
    In: Journal of Fungi, MDPI AG, Vol. 8, No. 7 ( 2022-06-28), p. 679-
    Abstract: The complex morphological structure of Aspergillus niger influences its production of proteins, metabolites, etc., making the genetic manipulation and clonal purification of this species increasingly difficult, especially in aconidial Aspergillus niger. In this study, we found that N-acetyl-D-glucosamine (GlcNAc) could induce the formation of spore-like propagules in the aconidial Aspergillus niger SH2 strain. The spore-like propagules possessed life activities such as drug resistance, genetic transformation, and germination. Transcriptomic analysis indicated that the spore-like propagules were resting conidia entering dormancy and becoming more tolerant to environmental stresses. The Dac1 gene and the metabolic pathway of GlcNAc converted to glycolysis are related to the formation of the spore-like propagules, as evidenced by the CRISPRi system, qPCR, and semi-quantitative RT-PCR. Moreover, a method based on the CRISPR-Cas9 tool to rapidly recycle screening tags and recover genes was suitable for Aspergillus niger SH2. To sum up, this suggests that the spore-like propagules are resting conidia and the mechanism of their formation is the metabolic pathway of GlcNAc converted to glycolysis, particularly the Dac1 gene. This study can improve our understanding of the critical factors involved in mechanisms of phenotypic change and provides a good model for researching phenotypic change in filamentous fungi.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    URL: Article
    DOI: 10.3390/jof8070679
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2784229-0
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