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1.
J Exp Bot ; 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33963382

RESUMO

Fractional vegetation cover (FVC) is the key trait of interest for characterizing crop growth status in crop breeding and precision management. Accurate quantification of FVC among different breeding lines, cultivars, and growth environments is a challenging task, especially because of the large spatiotemporal variability in complex field conditions. This study presents an ensemble modeling strategy for phenotyping crop FVC from unmanned aerial vehicle (UAV)-based multispectral images by coupling PROSAIL with gap probability model (PROSAIL-GP). Seven field experiments for four main crops were conducted, and canopy images were acquired using a UAV platform equipped with RGB and multispectral cameras. The PROSAIL-GP model successfully retrieved FVC in oilseed rape (Brassica napus L.) with coefficient of determination, root mean square error (RMSE), and relative RMSE (rRMSE) of 0.79, 0.09, and 18%, respectively. The robustness of the proposed method was further examined with rice (Oryza sativa L.), wheat (Triticum aestivum L.), and cotton (Gossypium hirsutum L.), and the high accuracy of FVC retrieval was obtained with rRMSE of 12%, 6%, and 6%, respectively. The findings suggest that the proposed method can efficiently retrieve crop FVC from UAV images at a high spatiotemporal domain, which would be a promising tool for precision crop breeding.

2.
Cells ; 10(5)2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33923029

RESUMO

Cystic fibrosis (CF) is caused by genetic mutations of the CF transmembrane conductance regulator (CFTR), leading to disrupted transport of Cl- and bicarbonate and CF lung disease featuring bacterial colonization and chronic infection in conducting airways. CF pigs engineered by mutating CFTR develop lung disease that mimics human CF, and are well-suited for investigating CF lung disease therapeutics. Clinical data suggest small airways play a key role in the early pathogenesis of CF lung disease, but few preclinical studies have focused on small airways. Efficient targeted delivery of CFTR cDNA to small airway epithelium may correct the CFTR defect and prevent lung infections. Adeno-associated virus 4 (AAV4) is a natural AAV serotype and a safe vector with lower immunogenicity than other gene therapy vectors such as adenovirus. Our analysis of AAV natural serotypes using cultured primary pig airway epithelia showed that AAV4 has high tropism for airway epithelia and higher transduction efficiency for small airways compared with large airways. AAV4 mediated the delivery of CFTR, and corrected Cl- transport in cultured primary small airway epithelia from CF pigs. Moreover, AAV4 was superior to all other natural AAV serotypes in transducing ITGα6ß4+ pig distal lung progenitor cells. In addition, AAV4 encoding eGFP can infect pig distal lung epithelia in vivo. This study demonstrates AAV4 tropism in small airway progenitor cells, which it efficiently transduces. AAV4 offers a novel tool for mechanistical study of the role of small airway in CF lung pathogenesis in a preclinical large animal model.

3.
Future Med Chem ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33928790

RESUMO

Aim: With the increasing abuse of antibacterial drugs, multidrug-resistant bacteria have become a burden on human health and the healthcare system. To find alternative compounds effective against hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA), novel derivatives of ocotillol were synthesized. Methods & Results: Ocotillol derivatives with polycyclic nitrogen-containing groups were synthesized and evaluated for in vitro antibacterial activity. Compounds 36-39 exhibited potent antibacterial activity against hospital-acquired MRSA, with MIC = 8-64 µg/ml. Additionally, a combination of compound 37 and the commercially available antibiotic kanamycin showed synergistic inhibitory effects, with a fractional inhibitory concentration index of ≤0.375. Conclusion: Compound 37 has a strong inhibitory effect, and this derivative has potential for use as a pharmacological tool to explore antibacterial mechanisms.

4.
J Am Chem Soc ; 143(15): 5826-5835, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33848163

RESUMO

Parastichy, the spiral arrangement of plant organs, is an example of the long-range apparent order seen in biological systems. These ordered arrangements provide scientists with both an aesthetic challenge and a mathematical inspiration. Synthetic efforts to replicate the regularity of parastichy may allow for molecular-scale control over particle arrangement processes. Here we report the packing of a supramolecular truncated cuboctahedron (TCO) into double-helical (DH) nanowires on a graphite surface with a non-natural parastichy pattern ascribed to the symmetry of the TCOs and interactions between TCOs. Such a study is expected to advance our understanding of the design inputs needed to create complex, but precisely controlled, hierarchical materials. It is also one of the few reported helical packing structures based on Platonic or Archimedean solids since the discovery of the Boerdijk-Coxeter helix. As such, it may provide experimental support for studies of packing theory at the molecular level.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33789071

RESUMO

In a new born pig cystic fibrosis (CF) model, the ability of gland-containing airways to fight infection was affected by at least two major host-defense defects: impaired mucociliary transport and a lower airway-surface liquid (ASL) pH. In the gland-containing airways, ASL pH is balanced by CFTR and ATP12A, which respectively control HCO3- transport and proton secretion. We found that, although porcine small airway tissue expressed little ATP12A, the ASL of epithelial cultures from CF distal small airways (diameter <200 µm) were nevertheless more acidic (compared to non-CF). Therefore, we hypothesized that gland-containing airways vs. small airways control acidification using distinct mechanisms. Our microarray data suggested that small airway epithelia mediate proton secretion via ATP6V0D2, an isoform of the V0d subunit of the H+-translocating plasma membrane V-type ATPase. Immunofluorescence of small airways verified the expression of the V0d2 subunit isoform at the apical surface of Muc5B+ secretory cells, but not ciliated cells. Inhibiting the V-type ATPase with bafilomycin A1 elevated the ASL pH of small airway cultures, in the presence or absence of HCO3-, and decreased ASL viscosity. These data suggest that, unlike large airways, which are acidified by ATP12A activity, small airways are acidified by V-type ATPase, thus identifying V-type ATPase as a novel therapeutic target for small airways diseases.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33724636

RESUMO

The construction of solid-state fluorescent materials with high quantum yield and good processability is of vital importance in the preparation of organic light-emitting devices. Herein, a series of tetraphenylethylene (TPE)-based multicomponent emissive metallacages are prepared by the coordination-driven self-assembly of tetra-(4-pyridylphenyl)ethylene, cis-Pt(PEt3 )2 (OTf)2 and tetracarboxylic ligands. These metallacages exhibit good emission both in solution and in the solid state because the coordination bonds and aggregation restrict the molecular motions of TPE synergistically, which suppresses the non-radiative decay of these metallacages. Impressively, one of the metallacages achieves very high fluorescence quantum yield (ΦF =88.46 %) in the solid state, which is further used as the coatings of a blue LED bulb to achieve white-light emission. The study not only provides a general method to the preparation of TPE-based metallacages but also explores their applications as solid-state fluorescent materials, which will promote the future design and applications of metallacages as useful emissive devices.

7.
Exp Clin Transplant ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736588

RESUMO

OBJECTIVES: Hemodynamic measurements during organ transplant procedures are essential. MATERIALS AND METHODS: In this observational study, we measured clinical and hemodynamic parameters in 11 patients with advanced pulse indicator continuous cardiac output monitoring. Normally distributed clinical data were calculated as means ± standard deviation; hemodynamic, metabolic, and respiratory parameters related to liver and renal function were compared by linear regression analysis using Pearson correlation. RESULTS: Compared with the normal range, systemic vascular resistance was high (2278.02 ± 719.6 dyne·s/cm²/m²) and intrathoracic blood volume was low (787.37 ± 224.01 mL/m²) in our patient group. C-reactive protein and interleukin 6 levels were 96.26 ± 68.10 mg/mL and 246.24 ± 355.74 mmol/L, respectively. Liver and renal function parameters were in normal ranges. Extravascular lung water was correlated with total, conjugated, and unconjugated bilirubin and albumin (r = 0.342/P = .005; r = 0.338/ P = .005; r = 0.394/P = .001, and r = 0.358/P = .003) but not with aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine. Intrathoracic blood volume index was correlated with total bilirubin, unconjugated bilirubin, and albumin (r = 0.324/P = .007; r = 0.394/P = .001, and r = 0.296/P = .015) but not with conjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine. Lactate was not correlated with total bilirubin, unconjugated bilirubin, albumin, and serum creatinine, but base excess was correlated with total bilirubin, unconjugated bilirubin, alanine aminotransferase, and albumin. PO2 and Pco2 were not correlated with liver function, although PO2 was correlated with albumin. CONCLUSIONS: No correlations were shown between intrathoracic blood volume index, extravascular lung water, and liver function, but metabolic parameters, including base excess and lactate, were correlated with liver function. Pulse indicator continuous cardiac output monitoring may be a useful method to assess organ function and tissue perfusion in organ transplant.

8.
Aging Cell ; : e13353, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780118

RESUMO

MicroRNAs (miRNAs) regulate gene expression and thereby influence cell development and function. Numerous studies have shown the significant roles of miRNAs in regulating immune cells including natural killer (NK) cells. However, little is known about the role of miRNAs in NK cells with aging. We previously demonstrated that the aged C57BL/6 mice have significantly decreased proportion of mature (CD27- CD11b+ ) NK cells compared with young mice, indicating impaired maturation of NK cells with aging. Here, we performed deep sequencing of CD27+ NK cells from young and aged mice. Profiling of the miRNome (global miRNA expression levels) revealed that 49 miRNAs displayed a twofold or greater difference in expression between young and aged NK cells. Among these, 30 miRNAs were upregulated and 19 miRNAs were downregulated in the aged NK cells. We found that the expression level of miR-l8la-5p was increased with the maturation of NK cells, and significantly decreased in NK cells from the aged mice. Knockdown of miR-181a-5p inhibited NK cell development in vitro and in vivo. Furthermore, miR-181a-5p is highly conserved in mice and human. MiR-181a-5p promoted the production of IFN-γ and cytotoxicity in stimulated NK cells from both mice and human. Importantly, miR-181a-5p level markedly decreased in NK cells from PBMC of elderly people. Thus, our results demonstrated that the miRNAs profiles in NK cells change with aging, the decreased level of miR-181a-5p contributes to the defective NK cell development and function with aging. This opens new strategies to preserve or restore NK cell function in the elderly.

9.
Molecules ; 26(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573149

RESUMO

The precise operation of molecular motion for constructing complicated mechanically interlocked molecules has received considerable attention and is still an energetic field of supramolecular chemistry. Herein, we reported the construction of two tris[2]pseudorotaxanes metallacycles with acid-base controllable molecular motion through self-sorting strategy and host-guest interaction. Firstly, two hexagonal Pt(II) metallacycles M1 and M2 decorated with different host-guest recognition sites have been constructed via coordination-driven self-assembly strategy. The binding of metallacycles M1 and M2 with dibenzo-24-crown-8 (DB24C8) to form tris[2]pseudorotaxanes complexes TPRM1 and TPRM2 have been investigated. Furthermore, by taking advantage of the strong binding affinity between the protonated metallacycle M2 and DB24C8, the addition of trifluoroacetic acid (TFA) as a stimulus successfully induces an acid-activated motion switching of DB24C8 between the discrete metallacycles M1 and M2. This research not only affords a highly efficient way to construct stimuli-responsive smart supramolecular systems but also offers prospects for precisely control multicomponent cooperative motion.


Assuntos
Compostos Organoplatínicos/química , Platina/química , Rotaxanos/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Éteres de Coroa/química , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Polímeros/síntese química , Polímeros/química , Rotaxanos/síntese química , Ácido Trifluoracético/química
10.
Bioorg Med Chem ; 34: 116054, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33571875

RESUMO

Tumor suppressor p53-binding protein 1 (53BP1), a tantem tudor domain (TTD) protein, takes part in DNA Damage Repair (DDR) pathways through the specific recognition of lysine methylation on histones. The dysregulation of 53BP1 is closely related to the development of many diseases including cancer. Moreover, recent studies found that deficiency of 53BP1 could increase the efficiency of precise CRISPR/Cas9 genome editing. Thus, discovery of inhibitor is beneficial to the study of biological functions of 53BP1 and the application of CRISPR/Cas9 genome editing. UNC2170 and its derivatives have been reported as 53BP1 targeted small molecular inhibitors with modest activities. Hence, to discover better 53BP1 inhibitors, we conducted an AlphaScreen assay based high-throughput screening (HTS) and identified a novel and effective 53BP1-TTD inhibitor DP308 which disrupts the binding between 53BP1 and H4K20me2 peptide with an IC50 value of 1.69 ± 0.73 µM. Both Microscale Themophoresis (MST) and Surface Plasmon Resonance (SPR) assays confirmed the direct binding between DP308 and 53BP1-TTD protein with binding affinity (Kd) of about 2.7 µM. Molecular docking studies further suggested that DP308 possibly occupies the H4K20me2 binding pocket of the 53BP1-TTD aromatic cage. These results demonstrated that DP308 is a promising small molecule inhibitor for further optimization towards a more potent chemical probe of 53BP1. Additionally, it could be a potential valuable tool for applying to gene editing therapy by increasing the efficiency of CRISPR/Cas9 genome editing.

11.
J Org Chem ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599126

RESUMO

Two organic cages have been prepared in situ in water through the 2 + 3 hydrazone coupling of two pyridinium-derived trialdehydes and oxalohydrazide. The highly water-soluble cages encapsulate and solubilize linear neutral molecules. Such encapsulation has been applied for the promotion of both two- or three-component hydrazone condensation in water. For two-component reactions, the yields of the resulting monohydrazones are increased from 5-10 to 90-96%. For three-component reactions of hydrazinecarbohydrazide with 11 aromatic aldehydes, in the presence of the organic cages, the bihydrazone products can be produced in 88-96% yields. In contrast, without the promotion of the organic cages, 9 of the reactions do not afford the corresponding dihydrazone product.

12.
Phys Rev Lett ; 126(3): 035301, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33543961

RESUMO

As in between liquid and crystal phases lies a nematic liquid crystal, which breaks rotation with preservation of translation symmetry, there is a nematic superfluid phase bridging a superfluid and a supersolid. The nematic order also emerges in interacting electrons and has been found to largely intertwine with multiorbital correlation in high-temperature superconductivity, where Ising nematicity arises from a four-fold rotation symmetry C_{4} broken down to C_{2}. Here, we report an observation of a three-state (Z_{3}) quantum nematic order, dubbed "Potts-nematicity", in a system of cold atoms loaded in an excited band of a hexagonal optical lattice described by an sp^{2}-orbital hybridized model. This Potts-nematic quantum state spontaneously breaks a three-fold rotation symmetry of the lattice, qualitatively distinct from the Ising nematicity. Our field theory analysis shows that the Potts-nematic order is stabilized by intricate renormalization effects enabled by strong interorbital mixing present in the hexagonal lattice. This discovery paves a way to investigate quantum vestigial orders in multiorbital atomic superfluids.

13.
J Am Chem Soc ; 143(2): 1224-1234, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33395279

RESUMO

Asymmetrical and dissymmetrical structures are widespread and play a critical role in nature and life systems. In the field of metallo-supramolecular assemblies, it is still in its infancy for constructing artificial architectures using dissymmetrical building blocks. Herein, we report the self-assembly of supramolecular systems based on two dissymmetrical double-layered ligands. With the aid of ultra-high-vacuum, low-temperature scanning tunneling microscopy (UHV-LT-STM), we were able to investigate four isomeric structures corresponding to four types of binding modes of ligand LA with two major conformations complexes A. The distribution of isomers measured by STM and total binding energy of each isomer obtained by density functional theory (DFT) calculations suggested that the most abundant isomer could be the most stable one with highest total binding energy. Finally, through shortening the linker between inner and outer layers and the length of arms, the arrangement of dissymmetrical ligand LB could be controlled within one binding mode corresponding to the single conformation for complexes B.

14.
Anticancer Drugs ; 32(3): 314-322, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33394687

RESUMO

Evodiamine (Evo), a quinazoline alkaloid and one of the most typical polycyclic heterocycles, is mainly isolated from Evodia rugulosa. Vasculogenic mimicry (VM) is a newly identified way of angiogenesis during tumor neovascularization, which is prevalent in a variety of highly invasive tumors. The purpose of this study was to investigate the effect and mechanism of Evo on VM in human colorectal cancer (CRC) cells. The number of VM structures was calculated by the three-dimensional culture of human CRC cells. Wound-healing was used to detect the migration of HCT116 cells. Gene expression was detected by reverse transcription-quantitative PCR assay. CD31/PAS staining was used to identify VM. Western blotting and immunofluorescence were used to detect protein levels. The results showed that Evo inhibited the migration of HCT116 cells, as well as the formation of VM. Furthermore, Evo reduced the expression of hypoxia-inducible factor 1-alpha (HIF-1α), VE-cadherin, VEGF, MMP2, and MMP9. In a model of subcutaneous xenotransplantation, Evo also inhibited tumor growth and VM formation. Our study demonstrates that Evo could inhibit VM in CRC cells HCT116 and reduce the expression of HIF-1α, VE-cadherin, VEGF, MMP2, and MMP9.

15.
Thorax ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472968

RESUMO

We recently identified epigallocatechin gallate (EGCG), a trihydroxyphenolic compound, as a dual inhibitor of lysyl oxidase-like2 and transforming growth factor-ß1 (TGFß1) receptor kinase that when given orally to patients with idiopathic pulmonary fibrosis (IPF) reversed profibrotic biomarkers in their diagnostic biopsies. Here, we extend these findings to advanced pulmonary fibrosis using cultured precision-cut lung slices from explants of patients with IPF undergoing transplantation. During these experiments, we were surprised to discover that not only did EGCG attenuate TGFß1 signalling and new collagen accumulation but also activated matrix metalloproteinase-dependent collagen I turnover, raising the possibility of slow fibrosis resolution with continued treatment.

16.
Eur J Med Chem ; 211: 113107, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33360797

RESUMO

Multidrug resistance (MDR) has become a major obstacle to malignancies treatment by chemotherapeutic drugs, therefore, it is important to develop MDR reversal agents with high activity. We have previously found that the hederagenin (HD) derivative HBQ showed good tumor MDR reversal activity in vitro and in vivo but had poor solubility. In this study, to enhance the aqueous solubility and tumor MDR reversal activity of HBQ, three series of HD derivatives were designed and synthesized. Nitrogen-containing heterocyclic-substituted, PEGylated, and ring-A substituted derivatives significantly reversed the MDR phenotype of KBV (multidrug-resistant oral epidermoid carcinoma) cells toward paclitaxel at a concentration of 10 µM in MTT assays. The PEGylated derivatives 10c-10e had increased aqueous solubility compared with HBQ by 18-657 fold, while maintaining tumor MDR reversal activity. The most in vitro active compound 10c possessed good chemical stability to an esterase over 24 h and enhanced the sensitivity of KBV cells to paclitaxel and vincristine with IC50 values of 4.58 and 0.79 nM, respectively. Mechanism studies indicated that compound 10c increased the accumulation of P-glycoprotein (P-gp) substrates rhodamine 123 and Flutax1 in KBV cells and MCF-7T (paclitaxel-resistant breast carcinoma) cells, that is to say, compound 10c exerted the reversal effect of tumor MDR by inhibiting the efflux function of P-gp. Finally, the structure-activity relationships were further investigated by analyzing the relationship between structure and tumor MDR reversal activity of HD derivatives. This study highlights the potential of PEGylated HD derivatives such as compound 10c for the development of tumor MDR reversal agents and provides information for the further improvement of the aqueous solubility and tumor MDR reversal activity of HD derivatives in the future.


Assuntos
Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Humanos , Estrutura Molecular , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Relação Estrutura-Atividade
17.
J Am Chem Soc ; 143(1): 399-408, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33371666

RESUMO

During the past few decades, fabrication of multistep fluorescence-resonance energy transfer (FRET) systems has become one of the most attractive topics within supramolecular chemistry, chemical biology, and materials science. However, it is challenging to efficiently prepare multistep FRET systems with precise control of the distances between locations and the numbers of fluorophores. Herein we present the successful fabrication of a two-step FRET system bearing specific numbers of anthracene, coumarin, and BODIPY moieties at precise distances and locations through an efficient and controllable orthogonal self-assembly approach based on metal-ligand coordination and host-guest interactions. Notably, the photosensitization efficiency and photooxidation activity of the two-step FRET system gradually increased with the number of energy transfer steps. For example, the two-step FRET system exhibited 1.5-fold higher 1O2 generation efficiency and 1.2-fold higher photooxidation activity than that of its corresponding one-step FRET system. This research not only provides the first successful example of the efficient preparation of multistep FRET systems through orthogonal self-assembly involving coordination and host-guest interactions but also pushes multistep FRET systems toward the application of photosensitized oxidation of a sulfur mustard simulant.

18.
J Am Chem Soc ; 143(1): 442-452, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33371675

RESUMO

The organization of molecular motors in supramolecular assemblies to allow the amplification and transmission of motion and collective action is an important step toward future responsive systems. Metal-coordination-driven directional self-assembly into supramolecular metallacycles provides a powerful strategy to position several motor units in larger structures with well-defined geometries. Herein, we present a pyridyl-modified molecular motor ligand (MPY) which upon coordination with geometrically distinct di-Pt(II) acceptors assembles into discrete metallacycles of different sizes and shapes. This coordination leads to a red-shift of the absorption bands of molecular motors, making these motorized metallacycles responsive to visible light. Photochemical and thermal isomerization experiments demonstrated that the light-driven rotation of the motors in the metallacycles is similar to that in free MPY in solution. CD studies show that the helicity inversions associated with each isomerization step in the rotary cycle are preserved. To explore collective motion, the trimeric motor-containing metallacycle was aggregated with heparin through multiple electrostatic interactions, to construct a multi-component hierarchical system. SEM, TEM, and DLS measurements revealed that the photo- and thermal-responsive molecular motor units enabled selective manipulation of the secondary supramolecular aggregation process without dissociating the primary metallacycle structures. These visible-light-responsive metallacycles, with intrinsic multiple rotary motors, offer prospects for cooperative operations, dynamic hierarchical self-assembled systems, and adaptive materials.

19.
Small ; 17(2): e2004142, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33326182

RESUMO

Hollow carbon-based nanoarchitectures (HCAs) derived from zeolitic imidazolate frameworks (ZIFs), by virtue of their controllable morphology and dimension, high specific surface area and nitrogen content, richness of metal/metal compounds active sites, and hierarchical pore structure and easy exposure of active sites, have attracted great interests in many fields of applications, especially in heterogeneous catalysis, and electrochemical energy storage and conversion. Despite various approaches that have been developed to prepare ZIF-derived HCAs, the hollowing mechanism has not been clearly disclosed. Herein, a specialized overview of the recent progress of ZIF-derived HCAs is introduced to provide an insight into their preparation strategy and the corresponding hollowing mechanisms. Based on the fundamental understanding of the structural evolution of ZIF nanocrystals during the high-temperature pyrolysis process, the hollowing mechanisms of ZIF-derived HCAs are classified into four categories: i) inward contraction of core-shell template@ZIF composites or hollow ZIFs, ii) outward contraction of ZIF@shell composites, iii) special outward contraction of ZIF arrays, and iv) mechanism beyond inward/outward contraction of pure ZIF nanocrystals. Finally, an outlook on the development prospects and challenges of HCAs based on ZIF precursors, especially in terms of controlled synthesis and future electrochemical application, is further discussed.

20.
IUBMB Life ; 73(2): 408-417, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33372396

RESUMO

Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), whether circular RNA (circRNA) is involved in this process remains unknown. In this study, we performed circRNA microarray profile and found an HBV-related circRNA, circ-ARL3 (hsa_circ_0092493). Stable knockdown of circ-ARL3 inhibited the proliferation and invasion of HBV+ HCC cells. High circ-ARL3 was positively correlated with malignant clinical features and poor prognosis. In terms of mechanism, HBx protein upregulated N6 -methyladenosine (m6 A) methyltransferases METTL3 expression, increasing the m6 A modification of circ-ARL3; then, m6 A reader YTHDC1 bound to m6 A-modified of circ-ARL3 and favored its reverse splicing and biogenesis. Furthermore, circ-ARL3 was able to sponge miR-1305, antagonizing the inhibitory effects of miR-1305 on a cohort of target oncogenes, thereby promoting HBV+ HCC progression. Importantly, depletion of circ-ARL3 significantly retarded HBV+ HCC cell growth in vivo, whereas this effect was evidently blocked after silencing of miR-1305. Collectively, our data suggest that circ-ARL3 is a critical regulator in HBV-related HCC, targeting the axis of circ-ARL3/miR-1305 may be a promising treatment for HBV+ HCC patients.

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