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Sirtuin 2 (SIRT2) regulates the maintenance of genome integrity by targeting pathways of DNA damage response and homologous recombination repair. However, whether and how SIRT2 promotes base excision repair (BER) remain to be determined. Here, we found that independent of its catalytic activity SIRT2 interacted with the critical glycosylase OGG1 to promote OGG1 recruitment to its own promoter upon oxidative stress, thereby enhancing OGG1 promoter activity and increasing BER efficiency. Further studies revealed that SIRT2 was phosphorylated on S46 and S53 by ATM/ATR upon oxidative stress, and SIRT2 phosphorylation enhanced the SIRT2-OGG1 interaction and mediated the stimulatory effect of SIRT2 on OGG1 promoter activity. We also characterized 37 cancer-derived SIRT2 mutants and found that 5 exhibited the loss of the stimulatory effects on OGG1 transcription. Together, our data reveal that SIRT2 acts as a tumor suppressor by promoting OGG1 transcription and increasing BER efficiency in an ATM/ATR-dependent manner.
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Proteínas Mutadas de Ataxia Telangiectasia , DNA Glicosilases , Reparo do DNA , Sirtuína 2 , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Humanos , Sirtuína 2/metabolismo , Sirtuína 2/genética , DNA Glicosilases/metabolismo , DNA Glicosilases/genética , Fosforilação , Regiões Promotoras Genéticas , Estresse Oxidativo , Ativação Transcricional , Células HEK293 , Dano ao DNA , Transcrição Gênica , Linhagem Celular Tumoral , Reparo por ExcisãoRESUMO
Reclamation of high-GWP near-azeotropic refrigerant R-410A (50 wt% R-32 (difluoromethane) + 50 wt% R-125 (pentafluoroethane)) can be an effective way to mitigate the greenhouse effect and achieve a circular economy. Efficient ionic liquids (ILs) as extractants needed to be found for the extractive distillation (ED) separation process of R-410A. Given the numerous combinations of cations and anions in ILs, the discovery of an efficient IL via experimental methods proves to be an exceedingly complex task. In this work, the solubilities of R-32, and R-125 in 840 conventional ILs (comprised of 20 cations and 42 anions) were analyzed based on infinite dilution activity coefficient. The absorption mechanisms of R-32 and R-125 in ILs were elucidated by analyzing excess enthalpy (HE), excess Gibbs free energy (GE)) and surface charge density distribution through COSMO-RS (Conductor-like Screening Model for Real Solvents). Results revealed that HE and GE of the mixture formed by R-125 and most ILs surpassed those of R-32, resulting in higher solubility of R-32 in most ILs compared to R-125. Structural changes of anions and cations had a greater effect on the solubility of R-125 in ILs. It is found for the first time that the existence of a strong hydrogen bond donor region in cations/anions generated intense repulsion with the hydrogen atom in R-125. Furthermore, a large area of weak polarity on the surface of cations/anions was difficult to form an effective charge shield with fluorine atoms in R-125, thus inhibiting the dissolution of R-125. Finally based on the identified interaction sites, combined with melting point and viscosity, some novel functional ILs with high selectivity for R-32 + R-125 were designed and determined for actual separation process. These findings significantly enrich the understanding of the solubility mechanism and provide theoretical guidance for designing new ILs for R-410A reclamation.
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Gases de Efeito Estufa , Líquidos Iônicos , Líquidos Iônicos/química , Ligação de Hidrogênio , Ânions/química , Cátions/químicaRESUMO
Sanguinoderma infundibulare is a newly discovered species of Ganodermataceae known to have high medicinal and ecological values. In this study, the whole-genome sequencing and comparative genomic analyses were conducted to further understand Ganodermataceae's genomic structural and functional characteristics. Using the Illumina NovaSeq and PacBio Sequel platforms, 88 scaffolds were assembled to obtain a 48.99-Mb high-quality genome of S. infundibulare. A total of 14,146 protein-coding genes were annotated in the whole genome, with 98.6% of complete benchmarking universal single-copy orthologs (BUSCO) scores. Comparative genomic analyses were conducted among S. infundibulare, Sanguinoderma rugosum, Ganoderma lucidum, and Ganoderma sinense to determine their intergeneric differences. The 4 species were found to share 4,011 orthogroups, and 24 specific gene families were detected in the genus Sanguinoderma. The gene families associated with carbohydrate esterase in S. infundibulare were significantly abundant, which was reported to be involved in hemicellulose degradation. One specific gene family in Sanguinoderma was annotated with siroheme synthase, which may be related to the typical characteristics of fresh pore surface changing to blood red when bruised. This study enriched the available genome data for the genus Sanguinoderma, elucidated the differences between Ganoderma and Sanguinoderma, and provided insights into the characteristics of the genome structure and function of S. infundibulare.
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Genoma , Genômica , Sequenciamento Completo do GenomaRESUMO
Wood-rotting fungi are organisms that can decompose wood substrates and extract nutrients from them to support their growth. They play a crucial role in the material cycle of forest ecosystems. The genus Pluteus plays a significant role in wood decomposition. In this study, the morphology and molecular systematics of the sect. Celluloderma of the genus Pluteus were carried out. Pluteusbrunneodiscus was identified as a new species, along with the discovery of two new records, P.cystidiosus and P.chrysophlebius, and a common species, P.romellii. Pluteusbrunneodiscus is characterized by the brown center of the pileus that transitions to white towards the margins, with the surface cracking to form irregular granules. It is typically found in Populus forests growing on decomposing twigs or wood chips. Line drawings, color photographs, and phylogenetic analyses of related species within the genus Pluteus accompany the descriptions of these four species. The analyses are based on ITS + TEF1-α sequence data. Finally, a key for the twenty species within the sect. Celluloderma of the genus Pluteus, which has been documented in China, is provided.
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BACKGROUND: Uni-compartmental knee replacement (UKR) is an alternative to total knee replacement for patients who have isolated compartment osteoarthritis. Studies have demonstrated that UKR can be safely performed as a day-case procedure without a negative impact on complication rates. The aim of this study was to compare the clinical outcomes between day-case and inpatient UKRs. METHODS: A single surgeon prospective case-controlled study was performed, comparing data between day-case UKRs and inpatient UKRs. This included longitudinal analysis of patient reported outcome measures (PROMs); including the Oxford Knee Score, Knee Injury and Osteoarthritis Outcome Score, Short Form 12-item Health Survey, EQ-5D-5L and the Self-administered Comorbidity Questionnaire. Post-operative pain scores (visual analogue scale), unplanned post-operative hospital reattendance rates and complications were also analysed. RESULTS: Overall, 100% of day-case patients were successfully discharged on the same day. Both inpatient (n = 23) and day-case (n = 23) UKRs demonstrated a significant within group longitudinal improvement of PROM scores (p < 0.05) following surgery. However, the post-operative PROM scores were significantly higher in the day-case group as compared to the inpatient group (p < 0.05). Both groups had comparable post-operative pain scores, but the day-case group demonstrated fewer unplanned reattendances and post-operative complications. CONCLUSION: The clinical outcomes of day-case UKR are superior to inpatient UKR. Careful patient selection and a robust multidisciplinary patient pathway are the key components to success of day-case joint replacement surgery. LEVEL OF EVIDENCE: Prospective Case-Control Study, level III.
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Osteoartrite do Joelho , Osteoartrite , Humanos , Pacientes Internados , Estudos de Casos e Controles , Articulação do Joelho , Dor Pós-Operatória , Osteoartrite do Joelho/cirurgia , Resultado do TratamentoRESUMO
Perenniporia is an important genus of Polyporaceae. In its common acceptation, however, the genus is polyphyletic. In this study, phylogenetic analyses on a set of Perenniporia species and related genera were carried out using DNA sequences of multiple loci, including the internal transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene (nLSU), the small subunit mitochondrial rRNA gene (mtSSU), the translation elongation factor 1-α gene (TEF1) and the b-tubulin gene (TBB1). Based on morphology and phylogeny, 15 new genera, viz., Aurantioporia, Citrinoporia, Cystidioporia, Dendroporia, Luteoperenniporia, Macroporia, Macrosporia, Minoporus, Neoporia, Niveoporia, Rhizoperenniporia, Tropicoporia, Truncatoporia, Vanderbyliella, and Xanthoperenniporia, are proposed; 2 new species, Luteoperenniporia australiensis and Niveoporia subrusseimarginata, are described; and 37 new combinations are proposed. Illustrated descriptions of the new species are provided. Identification keys to Perenniporia and its related genera and keys to the species of these genera are provided.
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Sanghuangporus refers to a group of rare medicinal fungi with remarkable therapeutic properties. However, current knowledge on the bioactive ingredients and antioxidant activities of different species of this genus is limited. In this study, a total of 15 wild strains from 8 species of Sanghuangporus were selected as the experimental materials for identification of the bioactive components (polysaccharide, polyphenol, flavonoid, triterpenoid, and ascorbic acid) and antioxidant activities (scavenging activities against hydroxyl, superoxide, DPPH, and ABTS radicals; superoxide dismutase activity; and ferric reducing ability of plasma). Notably, individual strains contained different levels of various indicators, among which Sanghuangporus baumii Cui 3573, S. sanghuang Cui 14419 and Cui 14441, S. vaninii Dai 9061, and S. zonatus Dai 10841 displayed the strongest activities. The correlation analysis of bioactive ingredients and antioxidant activities revealed that the antioxidant capacity of Sanghuangporus is mainly associated with the contents of flavonoid and ascorbic acid, followed by polyphenol and triterpenoid, and finally, polysaccharide. Together, the results obtained from the comprehensive and systematic comparative analyses contribute further potential resources and critical guidance for the separation, purification, and further development and utilization of bioactive agents from wild Sanghuangporus species, as well as the optimization of their artificial cultivation conditions.
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Wood-inhabiting fungi are abundant in China, but their distribution is uneven, with more fungi in southwest China and fewer fungi in northwest China. During the investigation of wood-inhabiting fungi in Xinjiang, we collected a large number of specimens. Eight specimens growing on Piceaschrenkiana were collected from Tianshan Mountains, and they were described as two new species in Ceriporiopsis and Sidera based on morphological characters and molecular evidence. Ceriporiopsistianshanensis is characterized by a cream to salmon-buff pore surface, larger pores measuring 1-3 per mm, and broadly ellipsoid basidiospores 5-6.5 × 3-4 µm. Sideratianshanensis is characterized by annual to perennial basidiocarps, measuring 15 mm thick, pores 5-7 per mm, cream to rosy buff pore surface, and allantoid basidiospores 3-3.5 × 1-1.4 µm. Detailed illustrations and descriptions of the novel species are provided.
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OBJECTIVES: Talaromyces marneffei is an emerging pathogen, and the number of infections in HIV-negative individuals is rapidly increasing. Nevertheless, there is no sufficient comprehensive report on this issue, and awareness needs to be raised among clinicians. METHODS: We analyzed the differences in the clinical data of patients who are HIV-negative and HIV-positive with Talaromyces marneffei infection (TMI) from 2018 to 2022. RESULTS: A total of 848 patients were included, among whom 104 were HIV-negative. The obvious differences between the HIV-positive and HIV-negative groups were as follows: (i) the patients who are HIV-negative were older and more likely to exhibit cough and rash, (ii) the time in days from symptom onset to diagnosis among patients who are HIV-negative was longer, (iii) the laboratory findings and radiological presentations seemed more severe in patients who are HIV-negative, (iv) differences were observed regarding the underlying conditions and co-infection pathogens, and correlation analysis showed that correlations existed for many indicators, (v) and persistent infection was more likely to occur in patients who are HIV-negative. CONCLUSION: TMI in patients who are HIV-negative differs from that in patients who are HIV-positive in many aspects, and more investigations are needed. Clinicians should be more aware of TMI in patients who are HIV-negative.
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Infecções por HIV , Micoses , Talaromyces , Humanos , Micoses/complicações , Micoses/diagnóstico , Micoses/microbiologia , Micoses/patologia , Estudos Retrospectivos , Infecções por HIV/complicações , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.
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OBJECTIVE: To evaluate and compare standard sperm parameters and sperm DNA fragmentation in seminal ejaculates from men whose partners had a history of recurrent pregnancy loss (RPL) and a control group of men who had recently established their fertility. METHODS: Semen samples from 85 patients with a history of RPL and 20 men with proven fertility were analyzed according to World Health Organization guidelines. Sperm DNA fragmentation was detected by sperm chromatin dispersion test (SCD). RESULTS: A significant difference (P< 0.05) was observed in sperm motility but not other parameters between the two groups. The mean number of sperm cells with fragmented DNA, represented as DNA fragmentation index, was significantly increased in the RPL group [(34.99± 14.62)%] compared with controls [(10.82± 4.80)%]. CONCLUSION: This study has indicated that sperm from men with a history of RPL have a higher incidence of DNA damage and poor motility compared with fertile males.
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Aborto Habitual/etiologia , Fragmentação do DNA , Motilidade dos Espermatozoides , Aborto Habitual/genética , Adulto , Dano ao DNA , Feminino , Humanos , Masculino , GravidezRESUMO
The genus Hydnellum is a kind of ectomycorrhizal fungi that can play a role in the material cycle by connecting the plant roots to the soil, and some species of Hydnellum are medicinal fungi with vital research value. The species diversity of Hydnellum is unclear in China. In this study, five new species of Hydnellum are described from China based on morphological characters and phylogenetic analyses inferred from two datasets of ITS + LSU and ITS + LSU + SSU + RPB2 sequences. H. chocolatum is characterized by its chocolate basidiomata with the fibrillose, spongy to tomentose pileal surface, and subglobose to globose basidiospores measuring (4.5-)5-6 × 4-5(-5.8) µm. H. concentricum is characterized by its zonate pileal surface, thin context, short stipe, presence of both simple septa and clamp connections in generative hyphae of spines, and subglobose to ellipsoidal basidiospores measuring (3.5-)4-5(-5.2) × (3.2-)3.5-5 µm. H. crassipileatum is characterized by its thick pileus with the reddish brown to grayish brown pileal surface, and subglobose to ellipsoidal basidiospores measuring 4-6(-6.5) × 4-5.5 µm. H. melanocarpum is characterized by its vinaceous brown to black pileus with spongy pileal surface, presence of both simple septa and clamp connections in generative hyphae of spines, and subglobose basidiospores measuring 4.5-5.5(-6) × (3.5-)3.8-5.1 µm. H. radiatum is characterized by its radially aligned stripes on pileal surface, grayish brown context, short stipe, and subglobose to ellipsoidal basidiospores measuring (3.5-)4-5 × 3-4.5(-5) µm. Full descriptions, illustrations, and phylogenetic trees to show the placement of the new species are provided.
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Electromechanical coupling plays a key role in determining the performance of stretchable strain sensor. Current regulation of the electromechanical coupling in stretchable strain sensor is largely restricted by the intrinsic mechanical properties of the device. In this study, a microfluidic strain sensor based on the core-shell package design with the auxetic metamaterial (AM) is presented. By overriding the mechanical properties of the device, the AM in the package effectively tunes the deformation of the microfluidic channel with the applied strain and configures the directional strain sensitivity with a large modulation range. The gauge factor (GF) of the strain sensor in the radial direction of the channel can be gradually shifted from the intrinsically negative value to a positive one by adopting the AMs with different designs. By simply replacing the AM in the package, the microfluidic strain sensor with the core-shell package can be configurated as an omnidirectional or directional stretchable strain sensor. With the directional sensitivity brought by the rational AM design, the application of the AM-integrated strain sensor in the skin-mounted tactile detection is demonstrated with high tolerance to unintended wrist movements.
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Microfluídica , PeleRESUMO
Xinjiang Uyghur Autonomous Region in China embraces a unique geographical and ecological environment, and the macrofungi represent a rich resource. However, few studies on the genus Pluteus have been reported from Xinjiang. In 2021, the macrofungal resources in Xinjiang were surveyed, and 10 specimens belonging to the genus Pluteus were collected. Based on the morphological study and molecular analysis, three species were recognized, P. aletaiensis, P. brunneidiscus, and P. hongoi. Pluteus aletaiensis is proposed as a new species. It is characterized by its bright yellow lamellae and stipe, brittle texture, subfusiform to vesicular pleurocystidia, with short pedicels to broadly lageniform to obtuse at apices, a hymeniderm pileipellis, containing dark brown intracellular pigment, and it grows on the ground. Pluteus brunneidiscus, a new record to China, is characterized by uneven, smooth, grayish brown to brown pileus, with an entire margin, and pointed or flatter apices intermediate cystidia, without apical hooks. Pluteus hongoi, a new record to Xinjiang Uyghur Autonomous Region, China, is characterized by the apical hook's structure (commonly bifid) of pleurocystidia. The nuclear internal transcribed spacer (nrITS) and translation elongation factor 1-alpha (TEF1-a) region were used for the molecular analysis. Phylogenetic trees were constructed using both the maximum likelihood analysis (ML) and Bayesian inference (BI). Detailed descriptions of the three species are presented herein. Finally, a key to the list of eight species of the genus Pluteus knew from Xinjiang is provided.
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Meio Ambiente , Filogenia , Teorema de Bayes , ChinaRESUMO
The family Boletaceae primarily represents ectomycorrhizal fungi, which play an essential ecological role in forest ecosystems. Although the Boletaceae family has been subject to a relatively global and comprehensive history of work, novel species and genera are continually described. During this investigation in northern China, many specimens of boletoid fungi were collected. Based on the study of their morphology and phylogeny, four new species, Butyriboletus pseudoroseoflavus, Butyriboletus subregius, Tengioboletus subglutinosus, and Suillellus lacrymibasidiatus, are introduced. Morphological evidence and phylogenetic analyses of the single or combined dataset (ITS or 28S, rpb1, rpb2, and tef1) confirmed these to be four new species. The evidence and analyses indicated the new species' relationships with other species within their genera. Detailed descriptions, color photographs, and line drawings are provided. The species of Butyriboletus in China were compared in detail and the worldwide keys of Tengioboletus and Suillellus were given.
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Rice starch properties of apparent amylose content (AAC), amylose content (AC), and amylopectin content (AP) are considered as the most important factors influencing grain quality as they are highly correlated with eating quality. This report is the first effort of predicting AC and AP values in rice flours, and recognizing waxy rice from non-waxy rice using NIRS technique. Calibration models generated by different mathematical, preprocessing treatments and combinations of wavelengths and signals were compared and optimized. The model established by modified partial least squares (MPLS) with "2, 8, 8, 2"/ Inverse MSC and â¼138 wavelengths signals yielded high RSQ of 0.977, 0.928, and 0.912 for AAC, AC and AP, respectively, as simultaneous measurement. MPLS-DA (discriminant analysis) could classify waxy and non-waxy rice with 100% accuracy. This high-throughput technology is valuable for breeding programs, and for the purposes of quality control in the food industry.
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Amilose , Oryza , Amilopectina/química , Amilose/química , Oryza/química , Melhoramento Vegetal , Espectroscopia de Luz Próxima ao Infravermelho , Amido/química , CerasRESUMO
The genetic diversity in 370 aromatic rice germplasms introduced from home and abroad, was investigated by using a total of 60 SSR markers. 361 alleles were detected, with the number of alleles (Na) per loci ranging from 2 to 10. The Nei's genetic diversity index (He) among loci varied widely from 0.104 at RM308 to 0.885 at RM2634 with an average value of 0.663. There was an obvious difference in SSR allelic diversity between indica and japonica rice. Indica rice showed more variation than japonica rice both for Na and He. Meanwhile, the genetic diversity of the landraces was higher than that of the improved varieties, and Na of the improved varieties was 86.5% of the landraces. Analysis of molecular variance indicated that 43.08% of the variation was from genetic differences between subspecies. It was also demonstrated that the genetic differentiation among different rice ecological regions ranged from 1.69% to 14.40%. There was significant differentiation between Southern China and Southwestern China, Central China and Southwestern China, respectively. Cluster analysis showed that 370 aromatic rice varieties were mainly classified into indica and japonica, and aromatic rice varieties from the same areas or the neighboring provinces were basically assigned to the same group.
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Variação Genética/genética , Oryza/genética , Análise por Conglomerados , Oryza/classificação , FilogeniaRESUMO
BACKGROUND: One of the main challenges for extrusion 3D bioprinting is the identification of non-synthetic bioinks with suitable rheological properties and biocompatibility. Our aim was to optimize and compare the printability of crystal, fibril and blend formulations of novel pulp derived nanocellulose bioinks and assess biocompatibility with human nasoseptal chondrocytes. METHODS: The printability of crystalline, fibrillated and blend formulations of nanocellulose was determined by assessing resolution (grid-line assay), post-printing shape fidelity and rheology (elasticity, viscosity and shear thinning characteristics) and compared these to pure alginate bioinks. The optimized nanocellulose-alginate bioink was bioprinted with human nasoseptal chondrocytes to determine cytotoxicity, metabolic activity and bioprinted construct topography. RESULTS: All nanocellulose-alginate bioink combinations demonstrated a high degree of shear thinning with reversible stress softening behavior which contributed to post-printing shape fidelity. The unique blend of crystal and fibril nanocellulose bioink exhibited nano- as well as micro-roughness for cellular survival and differentiation, as well as maintaining the most stable construct volume in culture. Human nasoseptal chondrocytes demonstrated high metabolic activity post printing and adopted a rounded chondrogenic phenotype after prolonged culture. CONCLUSIONS: This study highlights the favorable rheological, swelling and biocompatibility properties of nanocellulose-alginate bioinks for extrusion-based bioprinting.
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Alginatos/química , Bioimpressão , Celulose/química , Tinta , Nanopartículas/química , Impressão Tridimensional , Madeira/química , Biomassa , Sobrevivência Celular , Celulose/ultraestrutura , Condrócitos/citologia , Condrócitos/metabolismo , Reagentes de Ligações Cruzadas/química , Humanos , L-Lactato Desidrogenase/metabolismo , Nanopartículas/ultraestrutura , Septo Nasal/citologia , Reologia , Estresse Mecânico , ViscosidadeRESUMO
BACKGROUND: Commercially available tissue engineered skin remains elusive despite extensive research because the multi-stratified anisotropic structure is difficult to replicate in vitro using traditional tissue engineering techniques. Bioprinting, involving computer-controlled deposition of cells and scaffolds into spatially controlled patterns, is able to control not only the macro but also micro and nanoarchitecture and could offer the potential to more faithfully replicate native skin. METHODS: We conducted a literature review using PubMed, EMBASE and Web of Science for studies on skin 3D bioprinting between 2009 and 2016, evaluating the bioprinting technique, cell source, scaffold type and in vitro and in vivo outcomes. RESULTS: We outline the evolution of biological skin replacements, principles of bioprinting and how they apply to the skin tissue engineering field, potential clinical applications as well the current limitations and future avenues for research. Of the studies analysed, the most common types of bioinks consisted of keratinocytes and fibroblasts combined with collagen, although stem cells are gaining increasing recognition. Laser assisted deposition was the most common printing modality, although ink-jet and pneumatic extrusion have also been tested. Bioprinted skin promoted accelerated wound healing, was able to mimic stratified epidermis but not the thick, elastic, vascular dermis. CONCLUSIONS: Although 3D bioprinting shows promise in engineering skin, evidenced by large collective investments from the cosmetic industry, the research is still in its infancy. The resolution, vascularity, optimal cell and scaffold combinations and cost of bioprinted skin are hurdles that need to be overcome before the clinical applicability can be realised. Small scale 3D skin tissue models for cosmetics, drug and toxicity testing as well as tumour modelling are likely to be translated first before we see this technology used in reconstructive surgery patients.
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Bioimpressão/tendências , Impressão Tridimensional , Pele , Engenharia Tecidual/tendências , Humanos , Alicerces TeciduaisRESUMO
To avoid cell cycle arrest or apoptosis, rapidly proliferating cancer cells have to promote DNA double strand break (DSB) repair to fix replication stress induced DSBs. Therefore, developing drugs blocking homologous recombination (HR) and nonhomologous end joining (NHEJ) - 2 major DSB repair pathways - holds great potential for cancer therapy. Over the last few decades, much attention has been paid to explore drugs targeting DSB repair pathways for cancer therapy. Here, using 2 well-established reporters for analyzing HR and NHEJ efficiency, we found that both HR and NHEJ are elevated in hepatoma cell lines Hep3B and HuH7 compared with normal liver cell lines Chang liver and QSG-7701. Our further study found that Harmine, a natural compound, negatively regulates HR but not NHEJ by interfering Rad51 recruitment, resulting in severe cytotoxicity in hepatoma cells. Furthermore, NHEJ inhibitor Nu7441 markedly sensitizes Hep3B cells to the anti-proliferative effects of Harmine. Taken together, our study suggested that Harmine holds great promise as an oncologic drug and combination of Harmine with a NHEJ inhibitor might be an effective strategy for anti-cancer treatment.