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1.
Mater Sci Eng C Mater Biol Appl ; 107: 110246, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761158

RESUMO

Heparin-like polymers have a good anticoagulant effect due to some groups similar to heparin. Herein, sulfonated keratin(SK) was prepared by chain transfer radical polymerization of 3-sulfopropyl methacrylate(SPMA) to improve blood coagulation nature of keratin. Poly(ε-caprolactone)(PCL)/SK nanofibrous mats with the ratio of 7 and 3 were then fabricated by electrospinning. In vitro cytotoxicity and blood compatibility tests were performed to assess the biocompatibility. Viability of NIH 3T3 cells on PCL/SK mats was higher than that on the pristine PCL mats, indicating their good cytocompatibility. These sulfonated keratin-containing mats enhanced endothelial cell growth, while inhibited smooth muscle cell proliferation and reduced platelet adhesion in the presence of GSH and GSNO, as a result of NO generation. Furthermore, the biocomposite mats prolonged the activated partial thromboplastin time(APTT) effectively without hemolysis. Taken together, PCL/SK mats are potential for applications in vascular tissue engineering.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31774242

RESUMO

With the rapid development of minimally invasive techniques in orthopedics, minimally invasive surgery combined with injection of bone repair materials has attracted increasing attention for the treatment of bone defects. Inspired by material in mussels, we decorated nanohydroxyapatite (nHA) with dopamine (DA) to form polydopamine (PDA)-decorated nHA (PHA). Then, we introduced PHA into a Schiff base reaction of oxidized sodium alginate (OSA) and gelatin (Gel) to prepare an injectable bone repair hydrogel under mild conditions. Subsequently, the injectability, morphology, mechanical, swelling, and degradation properties of the hydrogel were studied. Then, bone marrow mesenchymal stem cells (BMSCs) were cocultured with the hydrogels to investigate the cytotoxicity, proliferation, and osteogenic differentiation properties of the hydrogel. Finally, the bone repair ability of the OSA-Gel-PHA hydrogels was explored using a 12 weeks rabbit bone defect model. The results of tube inversion and rheological test showed that the hydrogel gelation time was 3-7 min, which will be suitable for clinical operation. The results of SEM, compression tests, rheological tests, swelling and degradation properties tests showed that the addition of PHA changed the microstructure of the hydrogels from porous structure to layered structure, not only improved the compressive strength, toughness, elastic modulus, storage modulus of the hydrogels, but also reduced the swelling properties and degradation rate of the hydrogels, making it more conducive to clinical operations. The results of laser confocal, MTT assay, alkaline phosphatase (ALP) assay and in vivo animal experiments showed that the addition of PHA not only nontoxic, but also promoted the adhesion, proliferation and osteogenic differentiation of BMSCs, as well as the repair and maturation of bone. The application of injectable bone repair materials not only solves the problem of bone defect filling, but also avoids a series of complications caused by open surgery, providing new method for the treatment of bone defects.

3.
J Inorg Biochem ; 203: 110925, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31760233

RESUMO

Lead (Pb), which widely recognized as a nonessential heavy metal and a major environmental contamination, is a growing threat to the ecosystem and human body. In the present study, Malus micromalus Makino cv. 'Dong Hong' phenolic extract (MMPE) has been used to antagonise Pb-induced erythrocyte injury, hepatic and renal dysfunction in mice. Six-week-old male Kunming mice were gavaged with PbCl2 (20 mg/kg mouse/day) and/or MMPE (100 mg/kg mouse/day) by gavage administration for 10 days. We evaluated erythrocyte fragility, relative organ mass, biochemical parameters and histopathological changes to evaluate the protection effect of MMPE on the injury of liver and kidney in Pb-treated mice. MMPE significantly inhibited the increase of protein kinase C-α, B-cell lymphoma-2-associated X, cytochrome C and Caspase-3 protein levels and decreased calreticulin protein expression level in Pb-exposed mice. MMPE supplementation could maintain the integrity of erythrocyte membranes and ameliorate the endoplasmic reticulum stress in Pb-treated mice. It suggested MMPE as a natural nutritional supplement to alleviate Pb-induced hazardous effects in Pb-exposed humans.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31765320

RESUMO

The deep Q-network (DQN) and return-based reinforcement learning are two promising algorithms proposed in recent years. The DQN brings advances to complex sequential decision problems, while return-based algorithms have advantages in making use of sample trajectories. In this brief, we propose a general framework to combine the DQN and most of the return-based reinforcement learning algorithms, named R-DQN. We show that the performance of the traditional DQN can be significantly improved by introducing return-based algorithms. In order to further improve the R-DQN, we design a strategy with two measurements to qualitatively measure the policy discrepancy. We conduct experiments on several representative tasks from the OpenAI Gym and Atari games. The state-of-the-art performance achieved by our method with this proposed strategy validates its effectiveness.

5.
Biomed Pharmacother ; 121: 109565, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704615

RESUMO

With the improvement of people's living standard and the changes of environment, the incidence of diabetes mellitus (DM) is on the rise day by day, while clinical treatment mainly aims at lowering blood glucose, instead of fundamental prevention and treatment. What's worse, the measures of prevention and treatment of DM complications remain inadequate. Both Chinese and modern medicine have advantages and disadvantages in treating DM, therefore, it would be a worthy attempt to break through the bottleneck of DM treatment by combining the advantages of both, and explore the new measures to prevent and deal with DM from the perspective of the combination of Traditional Chinese Medicine (TCM) syndrome and modern medicine. In this paper, modern research methods and possible indicators of TCM syndromes of DM were expounded from clinical and basic research aspects, aiming to find specific biomarkers of TCM syndromes, and providing experimental supports for the diagnosis and treatment of DM and the verification of TCM theory.

6.
Medicine (Baltimore) ; 98(47): e17947, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764794

RESUMO

STUDY DESIGN: Clinical and radiographic results of a randomized, controlled, double-blind clinical trial OBJECTIVE:: To investigate the clinical applicability of a ball-point slide-type interbody distractor in posterior reduction and internal fixation for mid- to high-grade isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA: Posterior reduction and internal fixation is the effective treatment for spondylolisthesis. However, for the mid and high-grade isthmic spondylolisthesis patients with the conditions of vertebral osteoporosis and extremely narrow intervertebral space, the reduction is difficult; post-surgery intervertebral space height lost becomes serious; the fracture and loosening rate of fixation system is higher. No study regarding the prevention of these adverse outcomes in this technique is reported. METHODS: A total of 59 patients of mid and high-grade isthmic spondylolisthesis were randomly divided into random groups (investigational group and control group) applying simple randomized method in this study. In addition, 30 patients received posterior reduction and internal fixation as control. Twenty-nine patients received posterior reduction and internal fixation by ball-point slide-type interbody distractor were assigned to the investigational group. X-ray examination was performed before and after operation. The degree of reduction, height of intervertebral space were compared. The preoperative and postoperative Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were evaluated. Additionally, rate of the fixation system fracture was also assessed. RESULTS: Before treatment, there were no significant differences in ISH (P = .72), DR (P = .85), VAS of back pain (P = .55), VAS of leg pain (P = .83) and ODI (P = .68) were found between 2 groups. After 12-month treatment, there were no significant differences in ISH (P = .26), VAS of back pain (P = .09) and VAS of leg pain (P = .96) between two groups. Significant differences of DR (P = .02), ODI (P = .03) and adverse events (P = .00) were found between 2 groups. CONCLUSIONS: The results of this prospectively study showed that the ball-point slide-type interbody distractor in the posterior reduction and internal fixation produced good outcomes after 12-month treatment. More high quality randomized controlled trials and cases should still be needed to warrant the results of this study.

7.
Res Vet Sci ; 127: 42-46, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677415

RESUMO

The ORF3 protein of porcine epidemic diarrhea virus (PEDV) is found to function as an ion channel which influences virus virulence and production. Taking consideration of the importance of PEDV orf3 gene, we have performed comprehensive analysis to investigate its synonymous codon usage patterns. In this study, the results of base composition analysis showed A/T rich and G/C poor in PEDV orf3 genes, and the most abundant base was nucleotide T. The relative synonymous codon usage value in each codon revealed that codon usage bias existed. The mean ENC value of each gene was 48.75, indicating a low codon usage bias, as well as a relatively instable change in PEDV orf3 genes. The general correlation analysis between base composition and codon usage bias indicated that mutational bias has an impact on the PEDV codon usage bias. Neutral analysis suggested that natural selection pressure takes a more important influence than mutational bias in shaping codon usage bias. Moreover, other factors including hydrophobicity and aromaticity have been also found to influence the codon usage variation among the PEDV orf3 genes. This study not only represents the most systematic analysis of codon usage patterns in PEDV orf3 genes, but also provides a basic shaping mechanism of the codon usage bias.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31676070

RESUMO

Long noncoding RNAs (lncRNAs) play crucial roles in tumor development of osteosarcoma (OS). LncRNA PCAT6 was involved in the progression of multiple human cancers. However, the biological function of PCAT6 in OS remains largely unknown. We found that PCAT6 was elevated in OS tissues relative to that in their adjacent normal tissues. The upregulation of PCAT6 was positively associated with metastasis status and advanced stages and predicted poor overall and progression-free survivals in patients with OS. Functionally, silencing PCAT6 inhibited the proliferation, migration and invasion abilities of OS cells. Mechanistically, PCAT6, acting as a competitive endogenous RNA, upregulated expression of TGFBR1 and TGFBR2 to activate TGF-ß pathway via sponging miR-185-5p. This study uncovers a novel underlying molecular mechanism of PCAT6-miR-185-5p-TGFBR1/2-TGF-ß signaling axis in promoting tumor progression in OS, which indicates that PCAT6 may serve as a promising prognostic factor and therapeutic target again OS.

9.
BMC Neurol ; 19(1): 276, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703639

RESUMO

BACKGROUND: Internal carotid artery dissection has been well recognized as a major cause of ischaemic stroke in young and middle-aged adults. However, internal carotid artery dissection induced hypoglossal nerve palsy has been seldom reported and may be difficult to diagnose in time for treatment; even angiography sometimes misses potential dissection, especially when obvious lumen geometry changing is absent. CASE PRESENTATION: We report a 42-year-old man who presented with isolated hypoglossal nerve palsy. High-resolution MRI showed the aetiological dissected internal carotid artery. In addition, a potential genetic structural defect of the arterial wall was suggested due to an exon region mutation in the polycystic-kidney-disease type 1 gene. CONCLUSIONS: Hypoglossal nerve palsy is a rare manifestations of carotid dissection. High-resolution MRI may provide useful information about the vascular wall to assist in the diagnosis of dissection. High-throughput sequencing might be useful to identify potential cerebrovascular-related gene mutation, especially in young individuals with an undetermined aetiology.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31595704

RESUMO

Olanzapine, a second-generation atypical antipsychotic drug, is widely used for schizophrenia and moderate to severe mania associated with bipolar disorders. This open-label, randomized, single-dose, 2-sequence, 2-period crossover, comparative pharmacokinetic study assessed the bioequivalence of 5 mg of olanzapine administered in tablet (R) or disintegrating tablet (T) formulation in healthy Chinese volunteers under both fasting and fed conditions. Numbers of enrolled subjects were 30 and 24 for fasting and fed treatments, respectively. Blood samples were drawn and collected predose as well as up to 144 hours postdose. The plasma concentration of olanzapine was quantitated by a robust, rapid, and sensitive liquid chromatography-tandem mass spectrometry method. The R was bioequivalent to T formulation under either fasting or fed conditions. The 90%CI for ratios of the geometric means observed maximum plasma concentration, area under the curve from time 0 extrapolated to last time point, and area under the curve from time 0 extrapolated to infinity were all within the allowed limit (80.0% to 125.0%). The pharmacokinetic profiles of T and R formulations were similar under fasting and fed conditions. Both formulations were well tolerated, with a similar incidence of treatment-emergent adverse events under fasting and fed conditions.

11.
Nanoscale ; 11(42): 19806-19813, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31621752

RESUMO

Two new two-dimensional (2D) layered materials, namely, MgX2Se4 (X = Al, Ga) monolayers, are predicted to possess novel electronic properties. Ab initio electronic structure calculations show that both MgAl2Se4 and MgGa2Se4 monolayers are direct-gap semiconductors with bandgaps of 3.14 eV and 2.34 eV, respectively. The bandgap of both 2D materials is very sensitive to the in-plane biaxial strain, while the strain induced bandgap changes allow the tuning of optical absorption from the violet to green-light region. Also importantly, the in-plane electron mobility of both 2D materials is predicted to be as high as ∼0.7-1.0 × 103 cm2 V-1 s-1, notably higher than that of the MoS2 sheet (∼200 cm2 V-1 s-1), while it is comparable to that of black phosphorene (∼1000 cm2 V-1 s-1), suggesting their potential application in n-type field-effect transistors. Moreover, suitable bandgap and band-edge alignment make the monolayer MgX2Se4 a potential photocatalyst for water splitting. Lastly, we show that MgX2Se4 possesses a lower monolayer cleavage energy than that of graphite, indicating easy exfoliation of MgX2Se4 layers from their bulk.

12.
Nutr Cancer ; : 1-9, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31617767

RESUMO

Objective: To evaluate the prognostic value of modified Glasgow prognostic score (mGPS) asssessed prior to anticancer treatment in patients with esophageal squamous cell cancer (ESCC). Methods: A comprehensive search through PubMed, EMBASE, Web of Science and The Cochrane Library databases was performed to identify potential studies exploring the prognostic value of baseline mGPS in patients with ESCC. We combined the hazard ratios (HRs) with 95% confidence intervals (CIs) to assess the association of mGPS with overall survival (OS). Results: A total of 10 studies including 3415 patients were analyzed and all patients were from Japan or China. A significant correlation between elevated mGPS and poor OS (HR = 1.66, 95% CI: 1.14-2.41, P = 0.008) was observed. Subgroup analyses suggested that the country and therapy method may affect the effect of mGPS on predicting OS in ESCC and patients with mGPS 1 or two had poorer OS compared with those with mGPS 0 (HR = 2.91, 95% CI: 1.74-4.87, P<0.001; HR = 2.39, 95% CI: 1.44-3.97, P = 0.001). Conclusions: Baseline mGPS might serve as a promising indicator for the OS in Chinese and Japanese patients with ESCC. More well-designed prospective studies with large samples are needed to verify our findings.

13.
J Pharm Biomed Anal ; 178: 112812, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31639596

RESUMO

Drug induced liver injury (DILI) is a diverse set of liver injury occurring after exposure to any manufactured or naturally occurring chemical compounds. DILI has already become the leading cause of acute liver failure in developed countries. Early diagnosis is of great significance for the prevention and treatment of DILI, which can effectively avoid its progress to acute liver failure. In this paper, a novel targeted metabolomics method based on isobaric tagging reagent iTRAQ®-LC-MS/MS was developed for the exploring of 42 common amino acids and related amines alterations in rats treated with hydrazine, aiming to discover the potential biomarkers for early diagnosis of DILI. Forty-two amino acids and related amines were covered in this new method. Through derivatization by iTRAQ reagent, all derivatized amino acids and related amines can be separated and quantified in 16 min with excellent peak shape and good separation efficiency. Fragments related to reporter group (m/z 113 or 121) of iTRAQ reagents could be generated from all derivatized amino acids and related amines under general multiple reaction monitoring (MRM) parameters. Isotope dilution method was established for the quantification of amino acid, which significantly reduced the interference of matrix effect on quantitative accuracy. Using this iTRAQ®-LC-MS/MS method, the changes of amino acid metabolism were comprehensively investigated in rat serum and urine samples after DILI modeling by hydrazine. More significant changes of amino acids were observed in serum and urine samples with fold changes ranging from 0.5 to 193.7. Six significantly increased amino acids in serum, including L-citrulline, L-α-amino-adipic acid, L-tyrosine, L-glutamic acid, glycine and L-lysine, and ten amino acids and related amines in urine including L-citrulline, L-α-amino-adipic acid, L-tyrosine, taurine, ß-alanine, ethanolamine, argininosuccinic acid, D,L-ß-amino-isobutyric acid, γ-amino-n-butyric acid and L-glutamine, 3 of which were detected in both serum and urine. Except for L-lysine all these significantly increased amino acids and related amines possessed 92.5% to 100% specificity and sensitivity calculated at best cut-off points of their ROC curves in distinguishing control and DILI model group.

14.
J Pharm Biomed Anal ; 178: 112815, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31639597

RESUMO

The carboxyl group is the functional group in both bile acids (BAs) and fatty acids (FAs) (BAFAs). Considering the functional correlation and the structural similarity of these compounds, a sensitive and efficient method was developed here for the first time to simultaneously profile BAFAs based on ultrahigh performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Through optimization of the chromatographic conditions, all BAFAs can be efficiently separated and quantified in 19 min with excellent peak shape. For comprehensive profiling of endogenous FAs without standards, a strategy was established to predict the retention times (RTs) of all theoretically possible FAs on the basis of the good multiple linear regression relationship between RT and FA carbon chain length and double bond number. High-resolution mass spectrometry was employed for the final confirmation of these predicted FAs. Twenty-eight FAs in rat serum were newly identified using this strategy. Though the regulation of collision energies (CEs) for highly abundant compounds, the problems of their poor quantification linearity and accuracy caused by MS signal saturation were solved, facilitating the simultaneous quantification of both high- and low-abundance BAFAs with good linearity and accuracy. The established UPLC-MS/MS method was further used to quantify BAFAs in rat serum and to explore the disturbance of BAFA metabolism in the Tripterygium glycoside-induced liver injury rat model. A total of 25 BAs and 55 FAs in rat serum were identified and quantified. Several BAFAs, including nordeoxycholic acid, taurodeoxycholic acid and some unsaturated FAs, were found to differ significantly in the control and model groups. These BAFAs are very promising biomarkers for the evaluation of Tripterygium glycoside-induced liver injury.

15.
Biomolecules ; 9(10)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658691

RESUMO

As a disease characterized by severe liver necrosis and hemorrhage, duck viral hepatitis (DVH) is mainly caused by duck hepatitis A virus (DHAV). The positive-strand RNA genome of DHAV type 1 (DHAV-1) contains an internal ribosome entry site (IRES) element within the 5' untranslated region (UTR), structured sequence elements within the 3' UTR, and a poly(A) tail at the 3' terminus. In this study, we first examined that insulin-like growth factor-2 mRNA-binding protein-1 (IGF2BP1) specifically interacted with the DHAV-1 3' UTR by RNA pull-down assay. The interaction between IGF2BP1 and DHAV-1 3' UTR strongly enhanced IRES-mediated translation efficiency but failed to regulate DHAV-1 replication in a duck embryo epithelial (DEE) cell line. The viral propagation of DHAV-1 strongly enhanced IGF2BP1 expression level, and viral protein accumulation was identified as the key point to this increment. Collectively, our data demonstrated the positive role of IGF2BP1 in DHAV-1 viral proteins translation and provided data support for the replication mechanism of DHAV-1.

16.
J Am Chem Soc ; 141(45): 18334-18340, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31657909

RESUMO

Two-dimensional (2D) organic-inorganic perovskites (OIPs), with improved material stability over their 3D counterparts, are highly desirable for device applications. It is their considerable structural diversity that offers an unprecedented opportunity to engineer materials with fine-tuning functionalities. The isosteric substitution of hydrogen by an electronegative fluorine atom has been proposed as a useful route to improve the photovoltaic performance of 2D OIPs, whereas its valuable role in developing ferroelectricity is still waiting for further exploration. Herein, for the first time we applied fluorinated aromatic cations in extending the family of 2D OIP ferroelectrics, and successfully obtained [2-fluorobenzylammonium]2PbCl4 as a high-performance ferroelectric semiconductor. The failures in the nonferroelectric [4-fluorobenzylammonium]2PbCl4 and [3-fluorobenzylammonium]2PbCl4 demonstrate that the selective introduction of fluorine in correct structural positions is particularly essential. This work represents an unprecedented proof-of-concept in the use of fluorinated aromatic cations for the targeted design of excellent 2D OIP ferroelectrics, and is believed to inspire the future development of low-cost, high-efficiency, and stable device applications.

17.
J Biomed Mater Res A ; 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31606923

RESUMO

Vascular endothelial growth factor (VEGF) is an effective growth and angiogenic cytokine, which stimulates proliferation and survival of endothelial cells, and promotes angiogenesis and vascular permeability. Binding VEGF with heparin could protect it from rapid degradation, subsequently allowing it to be controlled release. Primarily, poly(ε-caprolactone) (PCL) and keratin were coelectrospun, followed by conjugating with heparin and subsequently binding VEGF. The loaded heparin and VEGF on these mats were quantified, respectively. The surface characteristics of mats were investigated by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The VEGF delivery results indicated these mats could sustainably release VEGF for 2 weeks. Cell viability assays suggested these mats were valid to accelerate human umbilical vein endothelial cells (HUVECs) proliferation, while inhibit human umbilical arterial smooth muscle cells (HUASMCs) growth under the combined actions of VEGF and heparin. The results tested by blood clotting times (APTT, PT, and TT), hemolysis, and platelet adhesion indicated the mats were blood compatible. To sum up, these biocomposite mats are ideal scaffolds for vascular tissue engineering.

18.
J Sep Sci ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613051

RESUMO

Alkaloids are important natural products that exhibit a wide spectrum of pharmacological activities. To efficiently separate and purify them, a rosin-based polymer-bonded silica stationary phase in high-performance liquid chromatography was synthesized via the surface radical polymerization of ethylene glycol maleic rosinate acrylate and methacrylic acid onto functionalized silica. The stationary phases, columns, optimization of chromatographic conditions for alkaloids, and thermodynamic behavior of the analytes on the column were fully studied. Under the optimized conditions, the prepared column efficiently purified natural camptothecine, caffeine, and evodiamine with the corresponding purities of 92, 96, and 97%. With this work, we have developed an efficient approach to isolate alkaloids and promoted the research on rosin-based materials in biomedicine and analytical chemistry.

19.
Org Lett ; 21(18): 7415-7419, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31486650

RESUMO

A remote stereocontrolled 1,8-conjugate addition of thiazolones to propargylic aza-p-quinone methides formed from propargylic alcohols has been developed with the aid of a chiral phosphoric acid, and this represents the first report on organocatalytic stereocontrolled 1,8-addition of propargylic aza-p-quinone methides. Notably, the remote stereocontrolled activation protocol enables the construction of vicinal sulfur-containing quaternary carbon stereocenters and axially chiral tetrasubstituted allenes and promotes the chemistry of chiral phosphoric acids.

20.
Org Biomol Chem ; 17(36): 8374-8378, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31486458

RESUMO

The first example of organocatalytic chemo-, regio- and enantioselective aza-Mannich reactions of triazoles and arylamines, respectively, with isatin-derived imines has been achieved in the presence of double hydrogen bonding organocatalysts, affording the valuable optically active 3-substituted 3-amino-2-oxindoles featuring N,N-ketal structural motifs in high yields. This strategy was featured by low catalyst loading, mild conditions, broad substrate scope, and high efficiency and selectivity.

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