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1.
Nat Commun ; 11(1): 792, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034155

RESUMO

Acyclic contiguous stereocenters are frequently seen in biologically active natural and synthetic molecules. Although various synthetic methods have been reported, predictable and unified approaches to all possible stereoisomers are rare, particularly for those containing non-reactive hydrocarbon substituents. Herein, a ß-boronyl group is employed as a readily accessible handle for predictable α-functionalization of enolates with either syn or anti selectivity depending on reaction conditions. Contiguous tertiary-tertiary and tertiary-quaternary stereocenters are thus accessed in generally good yields and diastereoselectivity. Based on experimental and computational studies, mechanism for syn selective alkylation is proposed, and Bpin (pinacolatoboronyl) behaves as a smaller group than most carbon-centered groups. The synthetic utility of this methodology is demonstrated by preparation of several key intermediates for bioactive molecules.

2.
Cell Death Differ ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015502

RESUMO

Angiogenesis plays crucial roles in maintaining the complex operation of central nervous system (CNS) development. The architecture of communication between neurogenesis and angiogenesis is essential to maintain normal brain development and function. Hence, any disruption of neuron-vascular communications may lead to the pathophysiology of cerebrovascular diseases and blood-brain barrier (BBB) dysfunction. Here we demonstrate that neural differentiation and communication are required for vascular development. Regarding the cellular and molecular mechanism, our results show that PRDM16 activity determines the production of mature neurons and their specific positions in the neocortex. In the cortical plate (CP), aberrant neurons fail to secrete modular calcium-binding protein 1 (SMOC1), an important neuronal signal that participates in neurovascular communication to regulate CNS angiogenesis. Neuronal SMOC1 interacts with TGFBR1 by activating the transcription factors phospho-Smad2/3 to convey intercellular signals to endothelial cells (ECs) in the TGF-ß-Smad signaling pathway. Together, our results highlight a crucial coordinated neurovascular development process orchestrated by PRDM16 and reveal the importance of intimate communication for building the neurovascular network during brain development.

3.
FEBS Open Bio ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053740

RESUMO

Iron overload affects the cell cycle of various cell types, but the effect of iron overload on human pluripotent stem cells (hPSCs) has not yet been reported. Here, we show that the proliferation capacities of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were significantly inhibited by ferric ammonium citrate (FAC) in a concentration-dependent manner. Additionally, deferoxamine (DFO) protected hESCs/hiPSCs against FAC-induced cell cycle arrest. However, iron overload did not affect pluripotency in hESCs/hiPSCs. Further, treatment of hiPSCs with FAC resulted in excess reactive oxygen species production and DNA damage. Collectively, our findings provide new insights into the role of iron homeostasis in the maintenance of self-renewal in hPSCs.

4.
Int J Hyg Environ Health ; 224: 113427, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31978725

RESUMO

BACKGROUND: Early life exposure to triclosan, an emerging endocrine disrupting chemical, may adversely impact childhood neurodevelopment, but limited epidemiologic studies have examined the associations. OBJECTIVE: We evaluated the associations between prenatal and postnatal triclosan exposure and child neurodevelopment at 3 years. METHODS: The study included 377 mother-child pairs who participated in Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. Triclosan concentrations in maternal and 3-year-old child urine samples were quantified using gas chromatography-tandem mass spectrometry (GC-MS/MS). Gesell Developmental Schedules (GDS) were used to assess child neurodevelopment at 3 years of age. Multivariate linear regression models were applied to estimate associations of prenatal and postnatal urinary triclosan concentrations with children's developmental quotients (DQs). RESULTS: Detection frequencies of triclosan in maternal and childhood urine samples were 100% and 99.5%, respectively. The median values of prenatal and postnatal urinary triclosan levels were 0.65 and 0.44 µg/L, respectively. One ln-unit increase of maternal urinary triclosan concentration was associated with increase of DQ scores in motor area of children (regression coefficient, ß = 0.28, 95% confidence interval, CI: 0.03, 0.54; p = 0.03). In sex-stratified analyses, maternal urinary triclosan levels were significantly related to increases in DQ scores in motor area among boys (ß = 0.25, 95%CI: 0.01, 0.50; p = 0.04), while postnatal urinary triclosan concentrations were inversely associated with DQ scores in social area in boys (ß = -0.37, 95%CI: -0.72, -0.03; p = 0.03). CONCLUSIONS: The findings suggested that prenatal triclosan exposure predicted increases in motor scores, while postnatal triclosan exposure was related to reductions in social scores of 3-year-old children. These associations were only observed in boys. The biological mechanisms linking triclosan exposure to neurodevelopment await further studies.

5.
Plant Cell ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996400

RESUMO

Meiosis consists of two highly conserved nuclear divisions, which allow eukaryotes to maintain their chromosome number through sexual reproduction. The successful completion of meiosis depends on homologous chromosome pairing. Centromere interactions during early meiotic prophase I facilitate homologous chromosome pairing, but the underlying mechanism is unclear. Here, we performed chromatin immunoprecipitation (ChIP)-mass spectrometry (MS) analysis of maize anthers during early meiotic prophase I using anti-CENH3 (centromeric histone H3) antibodies and determined that the cohesin subunit Structural Maintenance of Chromosome 3 (SMC3) interacts with CENH3 during this period. SMC3 is enriched at centromeres and along chromosome arms in threads from leptotene to pachytene and might promote interactions between homologous centromeres. We observed dysfunctional SMC3 assembly in meiotic-specific maize mutants with defective centromere pairing. In SMC3RNAi meiocytes, centromere pairing defects were observed during early meiotic prophase I, SMC3 was weakly associated with centromeres, and SMC3 did not localize to the chromosome arms. In wildtype mitosis, SMC3 is associated with chromatin and is enriched at centromeres from prophase to anaphase. CRISPR-CAS9-induced Zmsmc3 mutants showed premature loss of sister chromatid cohesion and mis-segregation of chromosomes in mitotic spreads. Our findings suggest that in addition to sister chromatid cohesion, ZmSMC3 participates in meiotic centromere pairing.

6.
ACS Appl Mater Interfaces ; 12(5): 6082-6089, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31939651

RESUMO

Advances in smart and wearable devices are driving innovations in multifunctional flexible materials at a tremendous pace. Here, drawing support from the unique flexible fluorophlogopite mica platform, we present a promising all-inorganic bendable Mn-modified 0.65(0.94Na0.5Bi0.5TiO3-0.06BaTiO3)-0.35SrTiO3 (NBBST) film with dual use in electrocaloric (EC) refrigeration and energy storage via a cost-effective transfer-free process. An appreciable room-temperature EC effect with adiabatic temperature change of 12 K and isothermal entropy of 18 J K-1 kg-1 was realized in the NBBST film, which benefits from the large change in dipolar ordering near depolarization temperature. Also, the film exhibits a broad operating temperature span over 25 °C because of its relaxor feature. Most importantly, the film can maintain a high EC performance either under bending deformation at 5 mm radius or after undergoing 104 bending-unbending cycles. Meanwhile, the flexible NBBST film possesses good energy storage property with a recoverable energy density of 56 J cm-3 and an efficiency of 66%. This is the first example of a lead-free all-inorganic multifunctional film capacitor toward the flexible EC refrigeration and energy storage devices. This work shows bright prospects in the emerging flexible e-market.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31953978

RESUMO

A strategically novel synthetic method for the fluoroarylation of allenic ester was successfully developed, which enables an expedient construction of a host of ß-fluoroalkyl-containing cinnamate derivatives. By resorting to visible light-promoted gold redox catalysis, this reaction proceeds smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups in excellent regio- and stereoselectivity. The concomitant activation mode for both allene motif and hydrogen fluoride is ascribed as the key for the success of this reaction.

8.
Mol Med Rep ; 21(2): 649-658, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974626

RESUMO

Osteosarcoma (OS) is the most common type of primary malignant bone tumor, which has a high incidence rate in children and adolescents. This research aims to reveal the role of long intergenic non­protein coding RNA 00460 (LINC00460) in OS by the loss­of­function experiment. LINC00460 is involved in the development of multiple types of tumor, but the role of LINC00460 in OS is unclear. To discover more effective molecular targets for the treatment of OS, the association between LINC00460 and OS prognosis was analyzed using the Gene Expression Profiling Interactive Analysis database. Additionally, small interfering RNA was used to knockdown LINC00460 gene expression in vitro to verify its biological effects on the viability, invasive and migratory potential of OS cells. LINC00460 knockdown significantly reduced the viability of OS cells and initiated cell cycle arrest within the G0/G1 phase through the decreased expression of cyclin D1 and CDK4/CDK6. In addition, LINC00460 knockdown promoted apoptosis of OS cells, and inhibited the migratory and invasive abilities of OS cells through the inhibition of the epithelial­mesenchymal transition pathway. In conclusion, the present study reported that LINC00460 may predict OS prognosis, and may serve an important role in mediating the viability, invasive and migratory potential of OS cells. Based on these findings, LINC00460 demonstrated promising potential as a future therapeutic target for OS treatment.

9.
Chin Med J (Engl) ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31985503

RESUMO

BACKGROUND: Clinical features and outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) remain controversial. Thus, we systematically reviewed literatures of clinical research to assess and analyze characteristics and prognosis of patients with HFmrEF. METHODS: PubMed, Embase, and Web of Science were searched for cohort studies up to April 23, 2019. Clinical features and multivariate adjusted hazard ratios (HRs) of endpoints of short-term all-cause mortality (SAM), long-term all-cause mortality (LAM), long-term cardiovascular death (LCD) and long-term HF rehospitalization (LHR) among patients with HFmrEF and HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) were well addressed. The primary outcome was LAM. RESULTS: Totally 19 studies were included in this study with 164,678 patients enrolled. The follow-up time of LAM was 3.6 ±â€Š2.5 years. HRs of LAM, SAM, LCD, LHR indicated that the risks of patients with HFmrEF were higher than HFpEF patients but lower than HFrEF patients, as for LAM, HFmrEF:HFpEF (reference) HR: 1.07, 95% confidence interval (CI): 1.00-1.15 (I = 63%, P = 0.0005); HFmrEF:HFrEF (reference) HR: 0.80, 95% CI: 0.73-0.88 (I = 70%, P < 0.0001). However, HFmrEF patients had the lowest rate in LAM (30.94%), SAM (2.57%), LCD (17.45%), LHR (26.36%) compared with the other two groups. CONCLUSIONS: This systematic review and meta-analysis compared features and prognosis between patients with HFmrEF and HFpEF, HFrEF by HRs. There appeared a special "separation phenomenon" showing rates of endpoints were inconsistent with their hazards in patients with HFmrEF compared with HFpEF patients.

10.
PLoS Biol ; 18(1): e3000582, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31995554

RESUMO

In most plants, centromeric DNA contains highly repetitive sequences, including tandem repeats and retrotransposons; however, the roles of these sequences in the structure and function of the centromere are unclear. Here, we found that multiple RNA sequences from centromeric retrotransposons (CRMs) were enriched in maize (Zea mays) centromeres, and back-spliced RNAs were generated from CRM1. We identified 3 types of CRM1-derived circular RNAs with the same back-splicing site based on the back-spliced sequences. These circular RNAs bound to the centromere through R-loops. Two R-loop sites inside a single circular RNA promoted the formation of chromatin loops in CRM1 regions. When RNA interference (RNAi) was used to target the back-splicing site of the circular CRM1 RNAs, the levels of R-loops and chromatin loops formed by these circular RNAs decreased, while the levels of R-loops produced by linear RNAs with similar binding sites increased. Linear RNAs with only one R-loop site could not promote chromatin loop formation. Higher levels of R-loops and lower levels of chromatin loops in the CRM1 regions of RNAi plants led to a reduced localization of the centromeric H3 variant (CENH3). Our work reveals centromeric chromatin organization by circular CRM1 RNAs via R-loops and chromatin loops, which suggested that CRM1 elements might help build a suitable chromatin environment during centromere evolution. These results highlight that R-loops are integral components of centromeric chromatin and proper centromere structure is essential for CENH3 localization.

11.
Carbohydr Polym ; 229: 115557, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826433

RESUMO

Chitosan (CS) based self-assembled nanohydrogels are considered as promising platform for biomedicine, petrochemical, agricultural and food applications due to their unique biodegradability, nano-interface effect, and intelligent responsiveness. However, the most CS derivatives are prepared in heterogeneous system, which is unstable and environmentally unfriendly. In this work, a series of hydroxybutyl chitosan (HBC) was synthesized based on a green and homogeneous system (potassium hydroxide (KOH)/urea), which given this derivative interesting temperature responsive phase transformation behavior. HBC could change from dissolved state into nanohydrogel state in deionized water, when the temperature exceed its critical phase change temperature, and this process could be repeated more than 50 cycles (one cycle/day) without coagulation. The nanohydrogels solution exhibited concentration and temperature-dependent ultraviolet absorption and visible light regulation, which had great application potential in smart windows. This study provided a novel preparation method and extended the application of chitosan-based temperature responsive self-assembled nanohydrogels.

12.
Chem Sci ; 10(37): 8701-8705, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31803445

RESUMO

A strategically novel single C-F bond functionalization of CF3-derived molecules, which shows a prominent advantage for the expedient construction of difluoromethylene-bridged organic scaffolds, is disclosed. The reported protocol consists of SN2' amination, N-alkylation and palladium-catalyzed allylic substitution reactions, which enables straightforward arylation and alkenylation of vinyltrifluoromethane derivatives. Furthermore, this strategy is characterized by its broad substrate scope with respect to both CF3-alkene and arylboronic acid derivatives.

13.
Appl Plant Sci ; 7(11): e11304, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31832286

RESUMO

Premise: We developed single-copy nuclear DNA markers for a perennial herb, Oreocharis auricula (Gesneriaceae), to help infer the evolutionary history of the genus Oreocharis in subtropical China. Methods and Results: We screened 834 putative single-copy nuclear genes from transcriptomes of 11 species of Primulina using the Illumina HiSeq 2000 platform. Based on the screening results, we developed 16 primer sets for accessions of O. auricula representing three wild populations. The number of alleles per locus ranged from three to 34. The levels of expected and observed heterozygosity varied from 0.000 to 0.372 and 0.000 to 0.650, respectively. The markers were successfully cross-amplified in the related species O. magnidens, O. speciosa, O. maximowiczii, and O. henryana. Conclusions: The newly developed markers will facilitate further studies on genetic diversity and phylogeographic structure throughout the distributional range of O. auricula. Additionally, these markers may be useful for other related species in Gesneriaceae.

14.
Huan Jing Ke Xue ; 40(8): 3753-3763, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854785

RESUMO

A total of 351 surface soil samples (0-20 cm) were collected from the Luanhe River Basin in Chengde City (a typical area of concentrated mineral resources) and analyzed for 12 heavy metals (Cu, Ni, Cd, Cr, Pb, Zn, Hg, V, Ti, Mn, As, and Co). The geochemical baseline values of the heavy metals were determined using the reference element method and the cumulative frequency curve method. Furthermore, the spatial structure and distribution characteristics of the heavy metals were assessed based on PCA and geostatistical analysis. The accumulation of heavy metal pollution in different types of soil and in association with different land use patterns was also evaluated using a geological accumulative index. The results showed that the geochemical baseline values of V, Ti, Cd, Pb, Mn, and Co in the surface soils of the Luanhe River Basin were higher than their background values for Hebei Province. In contrast, the geochemical baseline values of As, Zn, Cr, Cu, Ni, and Hg were lower than their background values. The average accumulation index of the surface soils followed the order of Cd > Pb > Cu > Ti > Mn > Zn > Cr > Ni > Co > V > Hg > As. More than 80% of the soil samples were categorized as having no accumulation or moderate accumulation of Pb, Ti, V, As, and Co, while over 70% of the soil samples were categorized as having no accumulation or moderate accumulation of Hg, Mn, Ni, Cu, As, Cd, and Cr. With respect to different soil types, the average accumulation index of heavy metals followed the order of fluvo-aquic soil>cinnamon soil>brown soil. With respect to land use types, the accumulation index of heavy metals followed the order of industrial and mining land > shrub forest land > agricultural land > woodland and grassland. The accumulation of Pb and Cd in the surface soils of agricultural land was relatively high in comparison to the other elements, with 27.69% and 25.38% of the samples being above the moderate accumulation level, respectively. The iron group elements Ti, V, Co, Ni, and Cr are likely to derive from naturally high geological background sources, while the spatial patterns of Cd, Pb, Zn, Mn, Cu, and As were associated with the combination of parent material and anthropogenic inputs. The accumulation of Hg was mainly influenced by human activities.

15.
Med Sci Monit ; 25: 8807-8813, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31749446

RESUMO

BACKGROUND Developmental dislocation of the hip (DDH) results in osteoarthritis in infants and children. This study aimed to investigate the effects of a single approach to arthroscopic reduction and debridement on clinical outcome in 12 infants with DDH. MATERIAL AND METHODS Twelve infants with irreducible DDH underwent single approach arthroscopic reduction and debridement followed by the use of a frog-leg position plaster cast with fixed flexion and abduction of the hips combined with external fixation for 6-8 weeks. Magnetic resonance imaging (MRI) or plain X-ray images were analyzed. Intra-articular obstructive factors for reduction were evaluated. The safety angle, medialization rate of the femoral head, and the acetabular angle were measured before and after arthroscopic reduction. RESULTS Imaging showed that the signs of DDH were significantly improved following arthroscopic reduction. Obstructive factors included hypertrophy of the round ligament, fibrous tissue and fat in the acetabular base, arthrocapsular constriction, and varus deformity of the hip. The safety angle was significantly increased following arthroscopic reduction (53.5°) compared with the safety angle before treatment (18.5°) (p<0.05). Medialization of the femoral head was significantly increased (127%) compared with that before treatment (72%) (p<0.05). Arthroscopic reduction significantly reduced the acetabular angle (25°) compared with that before treatment (37.5°) (p<0.05). CONCLUSIONS Single approach arthroscopic reduction and debridement was an effective method for treating DDH that significantly improved the medialization rate of the femoral head, acetabular angle, and the outcome of external fixation when a plaster cast was used with fixed flexion and abduction of the hips.

16.
Technol Cancer Res Treat ; 18: 1533033819883633, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31684829

RESUMO

OBJECTIVE: To investigate the effect of long noncoding RNA GM16343 on interleukin 36ß promotion of CD8+T cells in tumor microenvironment regulation. METHODS: The differentially expressed long noncoding RNA in interleukin 36ß-stimulated mouse CD8+T cells was screened by gene chip technology, and the significant differentially expressed long noncoding RNAs were verified by real-time polymerase chain reaction. The lentiviral vector that overexpresses or knockdown GM16343 was constructed, transfected into CD8+T cells, and stimulated with interleukin 36ß, and the amount of interferon γ secreted was detected by enzyme-linked immunosorbent assay. A mouse subcutaneous xenograft model that stably express interleukin 36ß was established, and the tumor size and mouse survival time were observed by stimulation with CD8+T cells overexpression or knockdown of GM16343. RESULTS: A total of 12 long noncoding RNAs with significant differences were screened by gene chip analysis. Real-time polymerase chain reaction showed that the difference in GM16343 was larger, and the difference between the groups was observed to be the most significant. Compared to control group, CD8+T cells overexpressing GM16343 increased the secretion of interferon γ, and the tumor diameter of the mice after stimulation showed significant reduction, and the survival time showed significant prolongation. Compared to control group, the CD8+T cells after GM16343 were knocked down. The interferon γ secretion was decreased, and no significant change in tumor diameter and survival time was observed. CONCLUSION: Interleukin 36ß may enhance antitumor immune response of CD8+T cells by regulating GM16343.

18.
Sci Rep ; 9(1): 16023, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690758

RESUMO

The ability of high-resolution NMR spectroscopy to readout the response of molecular interactions at multiple atomic sites presents a unique capability to define thermodynamic equilibrium constants and kinetic rate constants for complex, multiple-step biological interactions. Nonetheless, the extraction of the relevant equilibrium binding and rate constants requires the appropriate analysis of not only a readout that follows the equilibrium concentrations of typical binding titration curves, but also the lineshapes of NMR spectra. To best take advantage of NMR data for characterizing molecular interactions, we developed NmrLineGuru, a software tool with a user-friendly graphical user interface (GUI) to model two-state, three-state, and four-state binding processes. Application of NmrLineGuru is through stand-alone GUIs, with no dependency on other software and no scripted input. NMR spectra can be fitted or simulated starting with user-specified input parameters and a chosen kinetic model. The ability to both simulate and fit NMR spectra provides the user the opportunity to not only determine the binding parameters that best reproduce the measured NMR spectra for the selected kinetic model, but to also query the possibility that alternative models agree with the data. NmrLineGuru is shown to provide an accurate, quantitative analysis of complex molecular interactions.

19.
Plant J ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713923

RESUMO

The centromere, as an essential element to mediate chromosome segregation, is epigenetically determined by CENH3-containing nucleosomes as a functional marker; therefore the accurate deposition of CENH3 is crucial for chromosome transmission. We characterized the deposition of CENH3 in maize by over-expression and mutational analysis. Our results revealed that over-expressing CENH3 in callus is lethal while over-expressing GFP-CENH3 and CENH3-YFP in callus and plants is not and can be partly deposited normally. Different mutations of GFP-CENH3 demonstrated that CENH3-Thr4 in the N-terminus was needed for the deposition as a positive phosphorylation site and the last five amino acids in the C-terminus are necessary for deposition. The C-terminal tail of CENH3 is confirmed to be responsible for the interaction of CENH3 and histone H4, which indicates that CENH3 maintains deposition in centromeres via interacting with H4 to form stable nucleosomes. For GFP-CENH3 and CENH3-YFP, the fused tags at the termini probably affect the structure of CENH3 and reduce its interaction with other proteins, which in turn could decrease proper deposition. Taken together, multiple amino acids or motifs were shown to play essential roles in CENH3 deposition, which is suggested to be affected by numerous factors in maize.

20.
Int J Biol Macromol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739062

RESUMO

The effect of NaOH/urea solution freeze-thaw pretreatment to the chitosan of purity and the degree of deacetylation from the crab shell was examined. Higher purity chitosan (CS1) was prepared. On this basis, the raw materials after the first demineralization were pretreated with NaOH/urea solution freeze-thaw under different freeze-thaw situations. The produced chitosans (CS1-CS4) were characterized in the ash content, solubility, protein content, degree of deacetylation, viscosity average molecular weight, SEM, FTIR, XRD, antimicrobial activity. The results showed that the freeze-thaw process had advantageous influence on decreasing the ash content and increasing degree of deacetylation and antibacterial activity. Moreover, the antibacterial property of the extracted chitosans seemed to be positively related to their degree of deacetylation. It is concluded that CS4 had the lowest ash content (0.052%), the highest degree of deacetylation (86.02%) and the greatest antibacterial activity. Therefore, we recommend CS4 as agent for industrial and pharmaceutical applications.

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