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1.
J Chromatogr A ; : 460845, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31924329

RESUMO

Posaconazole represents a triazole antifungal agent which is used to treat various fungal infections. It contains four chiral centers leading to 16 stereoisomers. With the convergent synthesis route, only 11 related stereoisomeric impurities may potentially exist in the active pharmaceutical ingredient (API). It is a challenge to separate all the stereoisomers in one run. To address this problem, a multiple heart-cutting chiral-chiral two-dimensional liquid chromatography (2D-LC) method was developed. The multiple heart-cutting 2D-LC separation was implemented on 2D-LC system with three chiral columns with immobilized polysaccharide chiral stationary phases, namely Chiralpak IB, IC and IF3. In the system, the column Chiralpak IB was used as the 1D separation column and IC and IF3 columns were used parallelly for the 2D separation. The twelve stereoisomers were all well separated in one run by the multiple heart-cutting chiral-chiral 2D-LC system.

2.
Clin Exp Immunol ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901178

RESUMO

CD28H and B7-H5 have been identified as receptor-ligand pairs in B7/CD28 family, and have costimulatory activity in immune cells. Here, we have systematically reviewed the research reports on the CD28H/B7-H5 pathway. It was found that CD28H is mainly expressed in T cells and natural killer (NK) cells with naive and poorly differentiated properties, and repeated antigen stimulation leads to permanent loss of CD28H. In tumors, CD28H is mainly expressed in tissue-resident memory (TRM ) lymphocyte T cells, which is associated with improved tumor prognosis. B7-H5 is a ligand for CD28H and is widely expressed in tumor cells. B7-H5 expression is closely related to the prognosis of the tumor. Studies have shown that high expression of B7-H5 in tumor is related to a worse prognosis for lung cancer, osteosarcoma, oral squamous cell carcinoma (OSCC), breast carcinoma, human clear cell renal cell carcinoma (ccRCC), intrahepatic cholangiocarcinoma (ICC), bladder urothelial carcinoma (BUC) and colorectal cancer (CRC), but is associated with a better prognosis for pancreatic ductal adenocarcinoma (PDAC) and glioma. Controversial views exist in studies on gastric cancer prognosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31912612

RESUMO

A simple and ubiquitously present group, free amine, is used as directing group to synthesize the axially chiral biaryls by Pd(II)-catalyzed atroposelective C-H olefination. A broad range of axially chiral biaryl-2-amines are obtained in good yields with high enanioselectivities (up to 97% ee). Chiral spiro phosphoric acid (SPA) proved to be an efficient ligand and the loading could be reduced to 1 mol% without erosion of enantiocontrol in gram-scale synthesis. The resulting axially chiral biaryl-2-amines also provide a platform for the synthesis of a set of chiral ligands.

4.
Medicine (Baltimore) ; 99(2): e18692, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914069

RESUMO

RATIONALE: Allergic bronchopulmonary aspergillosis (ABPA) complicated with pulmonary thromboembolism (PTE) is rare. This report describes a patient who was diagnosed with ABPA and soon developed PTE. PATIENT CONCERNS: A 64-year-old man was diagnosed with ABPA in hospital for recurrent fever with cough. Two months later, the patient was readmitted to the hospital because of PTE. DIAGNOSES: ABPA was diagnosed during the first hospitalization, and laboratory tests showed an increase in serum IgE and Aspergillus fumigatus-specific IgG. Sputum culture suggested A. fumigatus and high-resolution computed tomography (HRCT) showed inflammation of both lungs and central bronchiectasis. During the second hospitalization, the patient's chest angiography showed PTE. INTERVENTIONS: The patient began treatment with antifungal drugs and corticosteroids, and was discharged from the hospital when his condition improved. Two months after discharge, the patient was treated with anticoagulant drugs due to PTE. OUTCOMES: The patient got better after taking anticoagulant drugs and was discharged from the hospital. The patient appears for regular follow-up visits in our outpatient clinic every 2 months and is currently in good condition. LESSONS: Patients with ABPA may be concurred with PTE. The risk of PTE in ABPA should be assessed in advance and preventive strategies also need to be taken beforehand. Pulmonary artery examination is necessary once it happened.

5.
Int J Mol Sci ; 21(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906317

RESUMO

The accumulation of fibrillar amyloid ß-protein (Aß) in blood vessels of the brain, the condition known as cerebral amyloid angiopathy (CAA), is a common small vessel disease that promotes cognitive impairment and is strongly associated with Alzheimer's disease. Presently, the clinical diagnosis of this condition relies on neuroimaging markers largely associated with cerebral macro/microbleeds. However, these are markers of late-stage disease detected after extensive cerebral vascular amyloid accumulation has become chronic. Recently, we generated a novel transgenic rat model of CAA (rTg-DI) that recapitulates multiple aspects of human CAA disease with the progressive accumulation of cerebral vascular amyloid, largely composed of Aß40, and the consistent emergence of subsequent microbleeds. Here, we investigated the levels of Aß40 in the cerebrospinal fluid (CSF) and plasma of rTg-DI rats as CAA progressed from inception to late stage disease. The levels of Aß40 in CSF and plasma precipitously dropped at the early onset of CAA accumulation at three months of age and continued to decrease with the progression of disease. Notably, the reduction in CSF/plasma Aß40 levels preceded the emergence of cerebral microbleeds, which first occurred at about six months of age, as detected by in vivo magnetic resonance imaging and histological staining of brain tissue. These findings support the concept that reduced CSF/plasma levels of Aß40 could serve as a biomarker for early stage CAA disease prior to the onset of cerebral microbleeds for future therapeutic intervention.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31944979

RESUMO

In this paper, we present a data-driven approach for modeling and animation of 3D necks. Our method is based on a new neck animation model, that decomposes the neck animation into local deformation caused by larynx motion and global deformation driven by head poses, facial expressions, and speech. A skinning model is introduced for modeling local deformation and underlying larynx motions, while the global neck deformation caused by each factor is modeled by its corrective blendshape set, respectively. Based on this neck model, we introduce a regression method to drive the larynx motion and neck deformation from speech. Both the neck model and the speech regressor are learned from a dataset of 3D neck animation sequences captured from different identities. Our neck model significantly improves the realism of facial animation and allows users to easily create plausible neck animations from speech and facial expressions. We verify our neck model and demonstrate its advantages in 3D neck tracking and animation.

7.
Zhongguo Fei Ai Za Zhi ; 23(1): 50-54, 2020 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-31948538

RESUMO

BACKGROUND: Da Vinci robotic system is currently widely used in thoracic surgery. The ports employment and procedures vary in different medical center in China. Usually, a small incision was used for assistant. METHODS: Based on clinical practice, we summarized domestic and foreign experience, combined with the characteristics of the Chinese body anatomy, employ portal technique and artificial pneumothorax, summarized a set of simplified and easier surgical method. RESULTS: Port-only artificial pneumothorax robot-assisted lobectomy has further improvement in anatomical safety, hemostatic effect and aesthetic appearance of the wound. CONCLUSIONS: This study optimizes the procedure of port-only artificial pneumothorax robot-assisted lobectomy in order to serve lung cancer patients better.

8.
J Pineal Res ; : e12631, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943334

RESUMO

In the elderly with atherosclerosis, hypertension, and diabetes, vascular calcification and ageing are ubiquitous. Melatonin (MT) has been demonstrated to impact the cardiovascular system. In this study we have shown that MT alleviates vascular calcification and ageing, and the underlying mechanism involved. We found that both osteogenic differentiation and senescence of vascular smooth muscle cells (VSMCs) were attenuated by MT in an MT membrane receptor-dependent manner. Moreover, exosomes isolated from VSMCs or calcifying vascular smooth muscle cells (CVSMCs) treated with MT could be uptaken by VSMCs and attenuated the osteogenic differentiation and senescence of VSMCs or CVSMCs, respectively. Moreover, we used conditional medium from MT treated VSMCs and transwell assay to confirm exosomes secreted by MT treated VSMCs attenuated the osteogenic differentiation and senescence of VSMCs through paracrine mechanism. We also found exosomal miR-204/miR-211 mediated the paracrine effect of exosomes secreted by VSMCs. A potential target of these two miRs was revealed to be BMP2. Furthermore, treatment of MT alleviated vascular calcification and ageing in 5/6-nephrectomy plus high phosphate diet treated (5/6 NTP) mice, while these effects were partially reversed by GW4869. Exosomes derived from MT-treated VSMCs were internalized into mice artery detected by in vivo fluorescence image, and these exosomes reduced vascular calcification and ageing of 5/6 NTP mice, but both effects were largely abolished by inhibition of exosomal miR-204 or miR-211. In summary, our present study revealed that exosomes from MT-treated VSMCs could attenuate vascular calcification and ageing in a paracrine manner through an exosomal miR-204/miR-211.

9.
Biomaterials ; 233: 119755, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927233

RESUMO

Photodynamic therapy (PDT) and chemotherapy has been applied as a prospective approach in tumor therapeutics. However, suffering from the inherent hypoxia status in tumor microenvironment (TME), the anticancer efficiency is enormously restricted, especially PDT. Herein, we develop a unique liposomal encapsulated catalase (CAT), lyso-targeted NIR photosensitizer (MBDP) and doxorubicin (Dox), forming FA-L@MD@CAT, to increase tumor oxygenation by catalyzing intratumoral high-expressed H2O2 for enhancing the combination of chemo-PDT. Moreover, the enhanced tumoral oxygenation not only facilitates singlet oxygen (1O2) production but also reverses immunosuppressive TME by modulating immune cytokines to favor antitumor immunities, which significantly induce tumor death. Notably, this system also realizes specific tumor recognition to folate receptor upregulated tumors and improves intratumoral accumulation. This work provides an effective strategy to promote tumor therapeutic index, which may possess a promising future in clinical application.

10.
Adv Healthc Mater ; : e1901201, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957291

RESUMO

Skin interstitial fluid (ISF) holds great potential as a highly desirable sample resource for point-of-care testing (POCT), where the key is to effectively collect target biomarkers from ISF. Hydrogel microneedle patch has great promise for ISF extraction. However, it is challenging to recover target biomarkers from the extracted skin ISF in hydrogel microneedle patches in an easy-administrated, fast, and bulky instrument-free manner. Herein, a hydrogel microneedle patch made of polyvinyl alcohol (PVA) and chitosan (CS) for POCT based on the ISF is developed. The phase transition property of PVA/CS hydrogel makes the microneedles stiff when dry, which is beneficial to easily penetrate into skin. Meanwhile, the highly porous microstructure of hydrogel offers good swelling ability for extraction of ISF and the thermal degradation property of PVA makes it convenient to quickly and efficiently recover target biomarkers from microneedle patch. The capability of this platform for POCT applications is further demonstrated by successful detections of typical biomarkers collected from the mimetic skin and monitoring the glucose level in rabbit skins during a day. The developed hydrogel microneedle patch holds the advantages of extraction of skin ISF and recovery of biomarkers, thus presenting as a powerful platform for skin ISF-based POCT applications.

11.
Trends Biotechnol ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31918858

RESUMO

Over the past few decades, PCR has been the gold standard for detecting nucleic acids (NAs) in various biomedical fields. However, there are several limitations associated with conventional PCR, such as complicated operation, need for bulky equipment, and, in particular, long thermocycling time. Emerging nanomaterials with photothermal effects have shown great potential for developing a new generation of PCR: ultrafast photonic PCR. Here, we review recent applications of photothermal nanomaterials in ultrafast photonic PCR. First, we introduce emerging photothermal nanomaterials and their light-to-heat energy conversion process in photonic PCR. We then review different photothermal nanomaterial-based photonic PCRs and compare their merits and drawbacks. Finally, we summarize existing challenges with photonic PCR and hypothesize its promising future research directions.

12.
Artif Cells Nanomed Biotechnol ; 48(1): 276-287, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31858826

RESUMO

Background: The abnormal expression Dopamine D1 receptor (DRD1) gives rise to the dysfunction of dopaminergic neurotransmitter and may be associated with the occurrence of schizophrenia. MicroRNAs (miRNAs) can regulate the DRD1 expression by binding 3'UTR and be involved in the post-transcriptional regulation.Methods: We first constructed the pmirGLO-recombined vectors of series of DRD1 gene 3'UTR-truncated fragments and performed the luciferase receptor assay to screen the underlying 3'UTR sequence targeted by miRNAs. Then, we predicted the potential miRNAs binding the target sequence and confirmed their effects using luciferase receptor assay after transfection of the miRNA mimics/inhibitors. We also examined the effects of the miRNA on the endogenous DRD1 expression.Results: We found that the DRD1 3'UTR ranging from -12 to +1135 bp was essential for the post-transcriptional regulation of miRNAs. The deletion of -12 to +154 bp fragment significantly increased the luciferase expression but not the mRNA expression. The miRNA-15a, miRNA-15b and miRNA 16 affected DRD1 expression in HEK293, U87, SK-N-SH and SH-SY5Y cell lines.Conclusion: The miRNA-15a, miRNA-15b and miRNA-16 inhibit the human dopamine D1 receptor expression by targeting 3'UTR -12 to +154 bp.HighlightsDRD1 3'UTR ranging from -12 to +1135 bp was essential for the post-transcriptional regulation of miRNAs.The deletion of -12 to +154 bp fragment significantly increased the luciferase expression but not the mRNA expression.The miRNA-15a, miRNA-15b and miRNA 16 affected DRD1 expression in different cell lines, respectively.

13.
Nano Lett ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31869236

RESUMO

Two-dimensional (2D) van der Waals (vdW) magnetic materials have recently been introduced as a new horizon in materials science, and they enable potential applications for next-generation spintronic devices. Here, in this communication, the observations of stable Bloch-type magnetic skyrmions in single crystals of 2D vdW Fe3GeTe2 (FGT) are reported by using in situ Lorentz transmission electron microscopy (TEM). We find the ground-state magnetic stripe domains in FGT transform into skyrmion bubbles when an external magnetic field is applied perpendicularly to the (001) thin plate with temperatures below the Curie temperature TC. Most interestingly, a hexagonal lattice of skyrmion bubbles is obtained via field-cooling manipulation with magnetic field applied along the [001] direction. Owing to their topological stability, the skyrmion bubble lattices are stable to large field-cooling tilted angles and further reproduced by utilizing the micromagnetic simulations. These observations directly demonstrate that the 2D vdW FGT possesses a rich variety of topological spin textures, being of great promise for future applications in the field of spintronics.

14.
ACS Appl Mater Interfaces ; 12(2): 2862-2870, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31850729

RESUMO

Among large numbers of transition metal dichalcogenides (TMDCs), monolayer rhenium disulfide (ReS2) is of particular interest due to its unique structural anisotropy, which opens up unprecedented opportunities in dichroic atomical electronics. Understanding the domain structure and controlling the anisotropic evolution of ReS2 during the growth is considered critical for increasing the domain size toward a large-scale growth of monolayer ReS2. Herein, by employing angle-resolved Raman spectroscopy, we reveal that the hexagonal ReS2 domain is constructed by six well-defined subdomains with each b-axis parallel to the diagonal of the hexagon. By further combining the first-principles calculations and the transmission electron microscopy (TEM) characterization, a dislocation-involved anisotropic evolution is proposed to explain the formation of the domain structures and understand the limitation of the domain size. Based on these findings, growth rates of different crystal planes are well controlled to enlarge the domain size, and moreover, single-crystal domains with a triangle shape are obtained. With the improved domain size, large-scale uniform, strictly monolayer ReS2 films are grown further. Scalable field-effect transistor (FET) arrays are constructed, which show good electrical performances comparable or even superior to that of the single domains reported at room temperature. This work not only sheds light on comprehending the novel growth mechanism of ReS2 but also offers a robust and controllable strategy for the synthesis of large-area and high-quality two-dimensional materials with low structural symmetry.

15.
J Org Chem ; 85(2): 994-1000, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31850754

RESUMO

Relebactam, a potent ß-lactamase inhibitor, in combination with Primaxin is an FDA-approved (Recarbrio) treatment for serious and antibiotic-resistant bacterial infections. An efficient synthesis of key chiral piperidine intermediate 1 suitable for large-scale preparation of relebactam is described. The key steps include a unique highly diastereoselective FeCl3·6H2O/NaBH4 reduction of a chiral oxime ether and chemoselective amidation of the resulting unprotected pipecolic acid. Nuclear magnetic resonance studies and density functional theory calculations were carried out on the substrate-Fe(III) complexes, which shed light on diastereoselective reduction.

16.
Trends Biochem Sci ; 45(2): 174-175, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31866304
17.
J Alzheimers Dis ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31796673

RESUMO

Exercise has been shown to be protective against the risk of dementias, including Alzheimer's disease (AD). Intervention studies have demonstrated its ability to mitigate cognitive and behavioral impairments and reduce disease in both humans and animals. However, information is lacking in regard to the volume and intensity, as well as timing of exercise onset with respect to disease stage, which produces optimal benefits. Here, utilizing the Tg2576 mouse, a model of AD-like parenchymal amyloid pathology and cognitive impairment, we sought to understand the effects of different lengths of daily access to a running wheel on advanced stage disease. This study is the first to determine the benefits of long-term exercise (4 months of voluntary running) and different periods of daily access to a running wheel (0 h, 1 h, 3 h, and 12 h running wheel access) beginning in 14-month-old Tg2576 mice, an age with significant amyloid pathology. We found that exercising Tg2576 animals showed lower levels of some aspects of AD pathology and reduced behavioral dysfunction compared to sedentary Tg2576 animals. High intensity exercise, rather than high volume exercise, was generally most beneficial in reducing amyloid pathology. Our results suggest that engaging in vigorous exercise programs, even after living a sedentary life, may lead to a measurable reduction in AD pathology and preservation of some cognitive abilities.

18.
HPB (Oxford) ; 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31822386

RESUMO

BACKGROUND: To investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs). METHOD: The TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined. RESULTS: Among 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P < 0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p = 0.05; TBS vs. number of tumors, p < 0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p = 0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p = 0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p = 0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p < 0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p < 0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p = 0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS. CONCLUSIONS: TBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone.

19.
Am J Gastroenterol ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31809301

RESUMO

OBJECTIVES: Constipation is prevalent in individuals after stroke. However, the pathophysiological mechanisms of poststroke constipation remain unclear. This study was designed (i) to investigate the difference in anorectal motility and rectal sensation among stroke patients with constipation, stroke patients without constipation, and healthy controls (HC), (ii) to evaluate the impact of stroke sites on constipation and rectal sensation, (iii) to explore the role of autonomic functions, and (iv) to determine the independent risk factors for poststroke constipation. METHODS: Seventy-one stroke patients and 24 HC were recruited. General information, clinical characteristics, and relevant questionnaires were collected. Meanwhile, an anorectal manometry test was performed to assess functions of anorectal motility and rectal sensation, and an electrocardiogram was recorded to evaluate autonomic functions. RESULTS: (i) Constipation patients exhibited increased rectal sensation thresholds, compared with patients without constipation or HC (P < 0.001). Almost no difference was detected in anorectal motility parameters among 3 groups. Constipation-associated clinical characteristics, such as spontaneous bowel movements, were weakly or moderately correlated with rectal sensation thresholds (P < 0.05 to P < 0.001 for various parameters). (ii) Patients with brainstem lesions had increased prevalence of constipation and first sensation threshold, compared with patients without brainstem lesions (P = 0.045, P = 0.025, respectively). (iii) There was a weak positive correlation between sympathetic activity and stroke severity and a weak negative one between vagal activity and stroke severity. Rectal sensation thresholds were positively and weakly correlated with sympathetic activity but negatively with vagal activity. (iv) The desire of defecation threshold and the physical activity were independent risk factors for poststroke constipation (P = 0.043, P = 0.025, respectively). DISCUSSION: Poststroke constipation is characterized by elevated thresholds for rectal sensation, rather than altered anorectal motility. Patients with brainstem lesions are predisposed to constipation possibly because of the disruption of afferent pathway from the rectum to the brain. Moreover, the desire of defecation threshold and the physical activity level are factors independently associated with poststroke constipation.

20.
Chin J Nat Med ; 17(11): 842-857, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31831131

RESUMO

Astrapterocarpan (AP) is a bioactive constituent of Astragali Radix and was selected as a model compound for investigating the in vitro metabolism of pterocarpans in this study. Its in vitro metabolism was conducted by incubation with rat hepatic 9000g supernatant (S9) in the presence of an NADPH-generating system. At first, four compounds were isolated and their structures were elucidated as 6a-hydroxy-AP (M1), astrametabolin I [M2, 1a-hydroxy-9, 10-dimethoxy-pterocarp-1(2), 4-diene-3-one], 9-demethyl-AP (M3, nissolin) and 4-methoxy-astraisoflavan (M4, 7, 2'dihydroxy-4, 3', 4'-trimethoxy-isoflavan) on the basis of NMR data, respectively. Among them, M1, M2 and M4 were new compounds. Next, the metabolite profile of AP in rat hepatic S9 was obtained via HPLC-DAD-ESI-IT-TOF-MSn, and 40 new metabolites were tentatively identified. These newly identified metabolites included 9 monohydroxylated metabolites, 1 demethylated metabolite, 7 demethylated and monohydroxylated metabolites, 4 dihydroxylated metabolites, 1 hydration metabolite, 1 didemethylated metabolite, 2 glucosylated metabolites, 1 monohydroxylated and dehydrogenated metabolite, 2 monohydroxylated and demethylated and dehydrogenated metabolites, 2 dimerized metabolites, 3 dimerized and monohydroxylated metabolites, 2 dimerized and didemethylated metabolites, and 5 dimerized and demethylated metabolites. Finally, the major metabolic reactions of AP in rat hepatic S9 were summarized and found to be hydroxylation, demethylation, dimerization, hydration, and dehydrogenation. More importantly, the biotransformation from AP to M2 and the dimerization of AP by incubation with hepatic S9 were reported for the first time. In conclusion, this is the first report on the metabolism of a pure pterocarpan in animal tissues, and these findings will provide a solid basis for further studies on the metabolism of other pterocarpans.

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