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1.
Molecules ; 26(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802584

RESUMO

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Several classes of compounds, such as amantadine and rimantadine have been testified for p7 inhibition. However, the efficacies of these compounds are not high. Here, we screened some novel p7 inhibitors with amantadine scaffold for the inhibitor development. The dissociation constant (Kd) of 42 ARD-series compounds were determined by nuclear magnetic resonance (NMR) titrations. The efficacies of the two best inhibitors, ARD87 and ARD112, were further confirmed using viral production assay. The binding mode analysis and binding stability for the strongest inhibitor were deciphered by molecular dynamics (MD) simulation. These ARD-series compounds together with 49 previously published compounds were further analyzed by molecular docking. Key pharmacophores were identified among the structure-similar compounds. Our studies suggest that different functional groups are highly correlated with the efficacy for inhibiting p7 of HCV, in which hydrophobic interactions are the dominant forces for the inhibition potency. Our findings provide guiding principles for designing higher affinity inhibitors of p7 as potential anti-HCV drug candidates.

2.
Mar Pollut Bull ; 167: 112292, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33873041

RESUMO

The effects of multiple natural and anthropogenic stressors on the functional trait composition and diversity of marine macrobenthic communities in Laoshan Bay were investigated using biological trait analysis (BTA). Seven traits, including 27 trait modalities and four functional diversity indices (functional richness, functional evenness, functional divergence, and Rao's quadratic entropy), were considered. The results of RLQ (environmental variables (R), species taxa (L), and traits (Q)) and variance partitioning analysis (VPA) showed that the trait compositions and functional diversity of macrobenthic communities were influenced by a combination of stressors, among which heavy metals were the major factors. At the sites with high heavy metal pollution, the prevalent traits were infauna, burrower, and deposit feeder, whereas epifauna, carnivores and crawlers were dominant at the sites of low heavy metal contamination. The impact of natural environmental gradients on macrobenthic communities is also worthy of attention.

3.
Nanomaterials (Basel) ; 11(3)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803677

RESUMO

Photothermal therapy (PTT) has received constant attention as an efficient cancer therapy method due to locally selective treatment, which is not affected by the tumor microenvironment. In this study, a novel 880 nm near-infrared (NIR) laser-triggered photothermal agent (PTA), 3TT-IC-4Cl, was used for PTT of a tumor in deep tissue. Folic acid (FA) conjugated amphiphilic block copolymer (folic acid-polyethylene glycol-poly (ß-benzyl-L-aspartate)10, FA-PEG-PBLA10) was employed to encapsulate 3TT-IC-4Cl by nano-precipitation to form stable nanoparticles (TNPs), and TNPs exhibit excellent photothermal stability and photothermal conversion efficiency. Furthermore, the in vitro results showed TNPs display excellent biocompatibility and significant phototoxicity. These results suggest that 880 nm triggered TNPs have great potential as effective PTAs for photothermal therapy of tumors in deep tissue.

4.
Nat Med ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888899

RESUMO

While CD19-directed chimeric antigen receptor (CAR) T cells can induce remission in patients with B cell acute lymphoblastic leukemia (ALL), a large subset relapse with CD19- disease. Like CD19, CD22 is broadly expressed by B-lineage cells and thus serves as an alternative immunotherapy target in ALL. Here we present the composite outcomes of two pilot clinical trials ( NCT02588456 and NCT02650414 ) of T cells bearing a 4-1BB-based, CD22-targeting CAR in patients with relapsed or refractory ALL. The primary end point of these studies was to assess safety, and the secondary end point was antileukemic efficacy. We observed unexpectedly low response rates, prompting us to perform detailed interrogation of the responsible CAR biology. We found that shortening of the amino acid linker connecting the variable heavy and light chains of the CAR antigen-binding domain drove receptor homodimerization and antigen-independent signaling. In contrast to CD28-based CARs, autonomously signaling 4-1BB-based CARs demonstrated enhanced immune synapse formation, activation of pro-inflammatory genes and superior effector function. We validated this association between autonomous signaling and enhanced function in several CAR constructs and, on the basis of these observations, designed a new short-linker CD22 single-chain variable fragment for clinical evaluation. Our findings both suggest that tonic 4-1BB-based signaling is beneficial to CAR function and demonstrate the utility of bedside-to-bench-to-bedside translation in the design and implementation of CAR T cell therapies.

6.
Nat Cell Biol ; 23(4): 424-436, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33820973

RESUMO

Although high-throughput RNA sequencing (RNA-seq) has greatly advanced small non-coding RNA (sncRNA) discovery, the currently widely used complementary DNA library construction protocol generates biased sequencing results. This is partially due to RNA modifications that interfere with adapter ligation and reverse transcription processes, which prevent the detection of sncRNAs bearing these modifications. Here, we present PANDORA-seq (panoramic RNA display by overcoming RNA modification aborted sequencing), employing a combinatorial enzymatic treatment to remove key RNA modifications that block adapter ligation and reverse transcription. PANDORA-seq identified abundant modified sncRNAs-mostly transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs)-that were previously undetected, exhibiting tissue-specific expression across mouse brain, liver, spleen and sperm, as well as cell-specific expression across embryonic stem cells (ESCs) and HeLa cells. Using PANDORA-seq, we revealed unprecedented landscapes of microRNA, tsRNA and rsRNA dynamics during the generation of induced pluripotent stem cells. Importantly, tsRNAs and rsRNAs that are downregulated during somatic cell reprogramming impact cellular translation in ESCs, suggesting a role in lineage differentiation.

7.
Ying Yong Sheng Tai Xue Bao ; 32(2): 763-770, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33650386

RESUMO

To explore the historical evolution and current status of the EwE (Ecopath with Ecosim) modelling research, the core dataset and extended dataset were collected by topic retrieval and citation indexing methods from the "Web of Science" from 1984 to 2020. The bibliometric analysis and mapping knowledge were performed by CiteSpace software, focusing on literature distribution, research forces, research theme, and hotspot evolution. The results showed that the annual publications in the EwE model researches were increasing, covering multi-disciplinary fields. Christensen, Walters, and Pauly were representative scholars with an important role in model development and relevant international cooperation. In the early stage, EwE model was usually applied to solve ecosystem problems, including spatial-temporal dynamic of structure and function, and the ecosystem effects of fisheries. Currently, marine resource management, ecosystem modelling, marine protected areas and ecosystem indicators had become the key themes. The research hotspots shifted from model development and food web structure to ecosystem forecasting and resource management, which would provide scientific evidence for ecosystem-based aquatic resource management and the construction of protected area in marine.


Assuntos
Bibliometria , Ecossistema , Pesqueiros , Cadeia Alimentar , Modelos Teóricos , Ovinos
8.
Medicine (Baltimore) ; 100(12): e25220, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761711

RESUMO

BACKGROUND: A growing number of studies suggest that lentinan combined with cisplatin thoracic injection for the treatment of lung cancer is an effective combination of traditional Chinese and Western medicine, which has a continuous and beneficial effect on eliminating clinical symptoms and improving cachexia in lung cancer patients. However, whether this treatment is effective and safe for lung cancer patients or not, evidence supporting the effectiveness and safety of this treatment is still incomplete. Besides, there is lack of systematic review to assess the detailed situation (including risk of bias and methodology) of current related clinical studies. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of lentinan combined with cisplatin thoracic injection in the treatment of lung cancer. METHODS: The major databases (Embase, PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database [VIP] Database, Chinese Biomedical Literature Service System [SinoMed], and Wanfang Database) were searched from inception to March 1, 2020. Randomized controlled trials (RCTs) of lentinan combined with cisplatin chest injection on patients with non-small cell lung cancer (NSCLC) were identified. Two assessors reviewed each trial independently. The methodological quality of the eligible studies was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias. Both the data extraction and the literature quality screening evaluation were conducted independently by 2 researchers. RESULTS: Totally 17 clinical RCTs were included in this study, involving 1390 patients. Meta-analysis results showed that the clinical efficacy (risk ratio [RR] = 1.34, 95% confidence interval [CI] 1.21-1.48), effective subgroup analysis (RR = 1.51, 95% CI 1.3-1.77), and quality of life (RR = 1.48, 95% CI 1.27-1.72), the differences are statistically significant. In terms of adverse reactions, mainly related to gastrointestinal reactions and bone marrow suppression, the incidence and degree of adverse reactions of lentinan combined with cisplatin thoracic injection group were lower than those of cisplatin thoracic injection group alone. CONCLUSIONS: The current evidence prompted that Lentinan combined with cisplatin in thoracic injection might benefit patients with NSCLC on a certain extent; this systematic review revealed some definite conclusions about the application of Lentinan combined with cisplatin in thoracic injection for NSCLC. Due to the low methodological quality, high risk of bias, and inadequate reporting on clinical data, these results still require verification by a large number of well designed, heterogeneous RCT studies. More rigorous, multicenter, sufficient-sample, and double-blind RCTs are warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Lentinano/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Catheter Cardiovasc Interv ; 97 Suppl 2: 1080-1088, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33780143

RESUMO

OBJECTIVES: We investigated whether the age shock index (SI) was associated with coronary plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI) using optical coherence tomography (OCT). BACKGROUND: The age SI is a simple clinical parameter that effectively predicts poor clinical outcomes among patients with STEMI. METHODS: This retrospective study evaluated 408 STEMI patients who underwent 3-vessel OCT during emergency percutaneous coronary interventions at a single center between January 2017 and October 2018. Patients were divided into groups with low or high age SI values (<41 vs. ≥41). Plaque characteristics were compared between the two groups for both culprit lesions (n = 408) and non-culprit lesions (n = 1,077). RESULTS: In culprit lesions, patients with a high age SI (≥41) were more likely to have plaque rupture (61.0% vs. 56.8%, p = .002) and thinner fibrous caps (fibrous cap thickness [FCT]: 40.0 [33.0-53.0] µm vs. 46.0 [36.0-63.8] µm, p = .021). In non-culprit lesions, patients with a high age SI were more likely to have high-risk plaques (29.9% vs. 17.8%, p = .018; simultaneous presence of a minimal lumen area of <3.5 mm2 , maximum lipid arc of >180°, FCT of <75 µm, and macrophage accumulation). Plaque-based analyses revealed that patients with a high age SI had larger lipid cores and lesser FCT. CONCLUSIONS: Patients with STEMI and a high age SI had increased risks of culprit plaque rupture and high-risk non-culprit plaques, and vulnerable plaque features at the culprit and non-culprit lesions. Therefore, a high age SI in patients with STEMI may indicate greater pancoronary vulnerability.

10.
J Transl Med ; 19(1): 123, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757550

RESUMO

BACKGROUND: As a common haematological malignancy, acute myeloid leukaemia (AML), particularly with extramedullary infiltration (EMI), often results in a high mortality rate and poor prognosis. Circular RNAs (circRNAs) regulate biological and pathogenic processes, suggesting a potential role in AML. We have previously described the overall alterations in circRNAs and their regulatory networks between patients with AML presenting with and without EMI. This study aims to find new prognostic and therapeutic targets potentially associated with AML. METHODS: qRT-PCR was performed on samples from 40 patients with AML and 15 healthy controls. The possibility of using circPLXNB2 (circRNA derived from PLXNB2) as a diagnostic and prognostic biomarker for AML was analysed with multiple statistical methods. In vitro, the function of circPLXNB2 was studied by lentivirus transfection, CCK-8 assays, flow cytometry, and Transwell experiments. Western blotting and qRT-PCR were performed to detect the expression of related proteins and genes. The distribution of circPLXNB2 in cells was observed using RNA fluorescence in situ hybridization (RNA-FISH). We also investigated the role of circPLXNB2 by establishing AML xenograft models in NOD/SCID mice. RESULTS: By analysing the results of qRT-PCR detection of clinical samples, the expression of the circPLXNB2 and PLXNB2 mRNAs were significantly increased in patients with AML, more specifically in patients with AML presenting with EMI. High circPLXNB2 expression was associated with an obviously shorter overall survival and leukaemia-free survival of patients with AML. The circPLXNB2 expression was positively correlated with PLXNB2 mRNA expression, as evidenced by Pearson's correlation analysis. RNA-FISH revealed that circPLXNB2 is mainly located in the nucleus. In vitro and in vivo, circPLXNB2 promoted cell proliferation and migration and inhibited apoptosis. Notably, circPLXNB2 also increased the expression of PLXNB2, BCL2 and cyclin D1, and reduced the expression of BAX. CONCLUSION: In summary, we validated the high expression of circPLXNB2 and PLXNB2 in patients with AML. Elevated circPLXNB2 levels were associated with poor clinical outcomes in patients with AML. Importantly, circPLXNB2 accelerated tumour growth and progression, possibly by regulating PLXNB2 expression. Our study highlights the potential of circPLXNB2 as a new prognostic predictor and therapeutic target for AML in the future.

11.
DNA Repair (Amst) ; 101: 103077, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33640758

RESUMO

The presence of uracil in DNA calls for rapid removal facilitated by the uracil-DNA glycosylase superfamily of enzymes, which initiates the base excision repair (BER) pathway. In humans, uracil excision is accomplished primarily by the human uracil-DNA glycosylase (hUNG) enzymes. In addition to BER, hUNG enzymes play a key role in somatic hypermutation to generate antibody diversity. hUNG has several isoforms, with hUNG1 and hUNG2 being the two major isoforms. Both isoforms contain disordered N-terminal domains, which are responsible for a wide range of functions, with minimal direct impact on catalytic efficiency. Subcellular localization of hUNG enzymes is directed by differing N-terminal sequences, with hUNG1 dedicated to mitochondria and hUNG2 dedicated to the nucleus. An alternative isoform of hUNG1 has also been identified to localize to the nucleus in mouse and human cell models. Furthermore, hUNG2 has been observed at replication forks performing both pre- and post-replicative uracil excision to maintain genomic integrity. Replication protein A (RPA) and proliferating cell nuclear antigen (PCNA) are responsible for recruitment to replication forks via protein-protein interactions with the N-terminus of hUNG2. These interactions, along with protein degradation, are regulated by various post-translational modifications within the N-terminal tail, which are primarily cell-cycle dependent. Finally, translocation on DNA is also mediated by interactions between the N-terminus and DNA, which is enhanced under molecular crowding conditions by preventing diffusion events and compacting tail residues. This review summarizes recent research supporting the emerging roles of the N-terminal domain of hUNG.

12.
Biomarkers ; 26(3): 260-267, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33523715

RESUMO

BACKGROUND: NCR3LG1 (B7-H6) protein is selectively overexpressed on tumour and is associated with fatal disease progression of various cancer. However, its prognostic value in bladder cancer (BCa) has not been well elaborated. METHODS: We examined the expression of NCR3LG1 in human BCa and analysed its clinical significance and prognostic value. Meanwhile, the expression of NCR3LG1 was intervened in human BCa cell line 253JBV to analyse subsequent effects on tumour. RESULTS: According to TCGA data, the disease-free survival rate was statistically significant between the NCR3LG1 high expression group and the low expression group (Log Rank p = 0.006). Immunohistochemical staining showed that the expression of NCR3LG1 in BCa tissue was significantly higher than that in adjacent tissues (p < 0.0001), which was positively correlated with TNM staging (p = 0.008), histological grade (p = 0.022), and lymphoma metastasis of BCa (p = 0.032). The proliferation (p < 0.0001), invasion (p < 0.001) and migration ability (p < 0.001) of 253JBV cells are significantly inhibited by knocking down the expression of NCR3LG1, and the cell cycle arrest is induced at the G1 phase, which accelerates the apoptosis of BCa cells (p < 0.005). CONCLUSION: Our findings indicate that NCR3LG1 is involved in the progression of human BCa and may become a potential prognostic biomarker for BCa.

13.
Invest New Drugs ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33566253

RESUMO

Our previous studies revealed that MYCN downregulates the expression of DKK3, activates the Wnt/ß-catenin signalling pathway at the transcriptional level, and thereby promotes the development of B cell acute lymphocytic leukaemia (B-ALL) but does not affect the methylation of the DKK3 promoter. Some studies have shown that MYCN is associated with histone acetylation. We speculate that histone deacetylase inhibitors (HDACis) can inhibit the Wnt/ß-catenin signalling pathway by inhibiting MYCN and increasing the expression of DKK3. Based on previous experiments, we tested this hypothesis by analysing the changes in MYCN, DKK3 and the Wnt/ß-catenin signalling pathways in B-ALL cells after treatment with the selective HDACi chidamide. The in vitro and in vivo experiments confirmed that chidamide inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of histone deacetylase, and these effects resulted in inhibition of the Wnt/ß-catenin signalling pathway and the proliferation of B-ALL cells. These findings indicate that chidamide might be used alone or in combination with other chemotherapy regimens for patients with B-ALL and thus provide a new approach to the treatment of B-ALL.

14.
BMC Dev Biol ; 21(1): 4, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33517884

RESUMO

BACKGROUND: Our previous study have shown that the PSMD11 protein was an important survival factor for cancer cells except for its key role in regulation of assembly and activity of the 26S proteasome. To further investigate the role of PSMD11 in carcinogenesis, we constructed a conditional exon 5 floxed allele of PSMD11 (PSMD11flx) in mice. RESULTS: It was found that homozygous PSMD11 flx/flx mice showed normal and exhibited a normal life span and fertility, and showed roughly equivalent expression of PSMD11 in various tissues, suggesting that the floxed allele maintained the wild-type function. Cre recombinase could induce efficient knockout of the floxed PSMD11 allele both in vitro and in vivo. Mice with constitutive single allele deletion of PSMD11 derived from intercrossing between PSMD11flx/flx and CMV-Cre mice were all viable and fertile, and showed apparent growth retardation, suggesting that PSMD11 played a significant role in the development of mice pre- or postnatally. No whole-body PSMD11 deficient embryos (PSMD11-/-) were identified in E7.5-8.5 embryos in uteros, indicating that double allele knockout of PSMD11 leads to early embryonic lethality. To avoid embryonic lethality produced by whole-body PSMD11 deletion, we further developed conditional PSMD11 global knockout mice with genotype Flp;FSF-R26CAG - CreERT2/+; PSMD11 flx/flx, and demonstrated that PSMD11 could be depleted in a temporal and tissue-specific manner. Meanwhile, it was found that depletion of PSMD11 could induce massive apoptosis in MEFs. CONCLUSIONS: In summary, our data demonstrated that we have successfully generated a conditional knockout allele of PSMD11 in mice, and found that PSMD11 played a key role in early and postnatal development in mice, the PSMD11 flx/flx mice will be an invaluable tool to explore the functions of PSMD11 in development and diseases.

15.
Genome Biol Evol ; 13(2)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33484557

RESUMO

Argyrosomus japonicus is an economically and ecologically important fish species in the family Sciaenidae with a wide distribution in the world's oceans. Here, we report a high-quality, chromosome-level genome assembly of A. japonicus based on PacBio and Hi-C sequencing technology. A 673.7-Mb genome containing 282 contigs with an N50 length of 18.4 Mb was obtained based on PacBio long reads. These contigs were further ordered and clustered into 24 chromosome groups based on Hi-C data. In addition, a total of 217.2 Mb (32.24% of the assembled genome) of sequences were identified as repeat elements, and 23,730 protein-coding genes were predicted based on multiple approaches. More than 97% of BUSCO genes were identified in the A. japonicus genome. The high-quality genome assembled in this work not only provides a valuable genomic resource for future population genetics, conservation biology and selective breeding studies of A. japonicus but also lays a solid foundation for the study of Sciaenidae evolution.

16.
J Pharm Biomed Anal ; 195: 113869, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33401116

RESUMO

An 1H NMR-based metabolomics approach was conducted to holisticly explore the effect of Xue Fu Zhu Yu (XFZY) capsule (a well-known Chinese herbal medicine) on high-fat diets combined with coronary artery ligation induced coronary heart disease (CHD) model rats. 1H NMR-based metabolomics approach combined with multivariate analysis was performed to explore potential biomarkers, a total of 20 metabolites were confirmed as contributors to the discrimination of model group and sham group. We investigated the dynamic metabolic characteristics of XFZY capsule on CHD rats, lactate, glutamine, pyruvate, citrate, choline and taurine were potential biomarkers of early effect. More potential biomarkers changed after 28 days of medication, XFZY capsules primarily influenced the taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, purine metabolism, glycolysis/gluconeogenesis, amino sugar and nucleotide sugar metabolism, primary bile acid biosynthesis.

17.
J Environ Manage ; 279: 111721, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33321355

RESUMO

This paper develops a dynamic interactive network slacks-based measure (SBM) model to assess the performance of regional industrial water systems (IWSs) in China. Such a system can be separated into a water use subsystem (WUS) and a wastewater treatment subsystem (WTS). Within this, wastewater and recycled water are interactive intermediate variables, and the capacity of facilities for treatment of wastewater (CTW) can be considered as a carry-over variable, reflecting dynamic components. Based on the proposed approach, we specify an evaluation technique for the subsystem, period, and subsystem period efficiencies. We apply the proposed approach to analyze the efficiencies of 30 regional IWSs in China during 2008-2014, and the results show the carry-over CTW has notable impacts on the overall efficiency of the IWS, especially on WTS efficiency. Only four regions are deemed overall efficient, namely, Beijing, Tianjin, Fujian, and Hainan. The inefficiency of the whole system arises from weaknesses in both the WUS and the WTS. It was found that the eastern area has the highest mean overall efficiency and mean subsystem efficiencies among the three major geographical areas of China.


Assuntos
Purificação da Água , Água , Pequim , China , Eficiência , Indústrias
18.
Nanomaterials (Basel) ; 10(12)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255734

RESUMO

Although photodynamic therapy (PDT) is an effective, minimally invasive therapeutic modality with advantages in highly localized and specific tumor treatments, large and deep-seated cancers within the body cannot be successfully treated due to low transparency to visible light. To improve the therapeutic efficiency of tumor treatment in deep tissue and reduce the side effects in normal tissue, this study developed a near-infrared (NIR)-triggered upconversion nanoparticle (UCNP)-based photosensitizer (PS) carrier as a new theranostics system. The NaYF4:Yb/Er UCNPs were synthesized by a hydrothermal method, producing nanoparticles of a uniformly small size (≈20 nm) and crystalline morphology of the hexagonal phase. These UCNPs were modified with folic acid-conjugated biocompatible block copolymers through a bidentate dihydrolipoic acid linker. The polymer modified hexagonal phase UCNPs (FA-PEAH-UCNPs) showed an improved dispersibility in the aqueous solution and strong NIR-to-vis upconversion fluorescence. The hydrophobic PS, pheophorbide a (Pha), was then conjugated to the stable vectors. Moreover, these UCNP-based Pha carriers containing tumor targeting folic acid ligands exhibited the significantly enhanced cellular uptake efficiency as well as PDT treatment efficiency. These results suggested that this system could extend the excitation wavelength of PDT to the NIR region and effectively improve therapeutic efficiency of PSs.

19.
Hematol Oncol ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33300153

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy. Understanding of the molecular pathogenesis may lead to novel therapeutic targets. Rapamycin, the mTOR inhibitor, showed inhibitory effects on T-ALL cells. In this study, we showed that rapamycin significantly reduced MYCN mRNA and protein in a concentration-dependent manner in T-ALL cells. Selective knockdown of MYCN by small interfering RNA had similar effects to rapamycin to inhibit T-ALL proliferation and colony formation and to induce G1-phase cell-cycle arrest and apoptosis. The inhibitory effects of rapamycin and MYCN depletion were also found in a Molt-4 xenograft model. Rapamycin and MYCN inhibition suppressed both Wnt/ß-catenin and mTOR signaling pathways. The results suggest the effects of rapamycin on adult T-ALL is likely mediated by downregulation of MYCN. The findings suggest MYCN a potential target for the treatment of adult T-ALL. Additionally, dual-targeting of mTOR and Wnt/ß-catenin pathways may represent a novel strategy in the treatment of adult T-ALL. This article is protected by copyright. All rights reserved.

20.
PLoS One ; 15(12): e0244495, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373404

RESUMO

Species distribution monitoring and biomass assessment are crucial for fishery management and resource conservation. However, traditional methods such as motor trawling are costly and less effective than the novel environmental DNA (eDNA) approach. This study employs eDNA approach to investigate horizontal and vertical distributions of small yellow croaker (Larimichthys polyactis), an economically important species, in the East China Sea. The analysis of 171 eDNA samples collected from 44 stations using the species-specific primers and Taqman probe suggests a presence of small yellow croaker at 28 sampling layers in 44 stations. Significant differences in croaker eDNA concentrations were revealed among sampling stations and layers, consistent with previous findings through motor-trawl capture offshore and nearshore ichthyoplakton surveys, indicating small yellow croaker exhibits strong regional distribution and layer preference. In addition, we found a high eDNA concentration of small yellow croaker in the surface waters beyond the motor-trawl prohibition line, which confirms spawning grounds have been expanded from nearshore to offshore areas. Such expansion of spawning grounds could be a response by small yellow croaker to stressors such as overfishing, climate change, and nearshore environment contamination. To identify environmental variables potentially associated with small yellow croaker presence and absence, we conducted a correlation analysis between eDNA concentration and environmental variables, and the results provide a guideline for further investigation of fishery resources in the future. In conclusion, this study demonstrates the power of the eDNA approach in monitoring small yellow croaker at extensive geographic scales. The developed protocols and the findings are expected to assist in long-term monitoring and protection programs and benefit sustainable fishery in small yellow croaker.


Assuntos
Conservação dos Recursos Naturais , Monitorização de Parâmetros Ecológicos/métodos , DNA Ambiental/isolamento & purificação , Pesqueiros/estatística & dados numéricos , Perciformes/genética , Distribuição Animal , Animais , China , Estudos de Viabilidade , Água do Mar/química
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