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Nitrate (NO3 - ) is crucial for optimal plant growth and development and often limits crop productivity under low availability. In comparison with model plant Arabidopsis, the molecular mechanisms underlying NO3 - acquisition and utilization remain largely unclear in maize. In particular, only a few genes have been exploited to improve nitrogen use efficiency (NUE). Here, we demonstrated that NO3 - -inducible ZmNRT1.1B (ZmNPF6.6) positively regulated NO3 - -dependent growth and NUE in maize. We showed that the tandem duplicated proteoform ZmNRT1.1C is irrelevant to maize seedling growth under NO3 - supply; however, the loss of function of ZmNRT1.1B significantly weakened plant growth under adequate NO3 - supply under both hydroponic and field conditions. The 15 N-labelled NO3 - absorption assay indicated that ZmNRT1.1B mediated the high-affinity NO3 - -transport and root-to-shoot NO3 - translocation. Transcriptome analysis further showed, upon NO3 - supply, ZmNRT1.1B promotes cytoplasmic-to-nuclear shuttling of ZmNLP3.1 (ZmNLP8), which co-regulates the expression of genes involved in NO3 - response, cytokinin biosynthesis and carbon metabolism. Remarkably, overexpression of ZmNRT1.1B in modern maize hybrids improved grain yield under N-limiting fields. Taken together, our study revealed a crucial role of ZmNRT1.1B in high-affinity NO3 - transport and signalling and offers valuable genetic resource for breeding N use efficient high-yield cultivars.
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Arabidopsis , Nitrógeno , Nitrógeno/metabolismo , Nitratos/metabolismo , Zea mays/genética , Zea mays/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fitomejoramiento , Arabidopsis/genética , Raíces de Plantas/metabolismoRESUMEN
Histological transformation into an aggressive B-cell lymphoma indicates a poor survival outcome for patients with indolent marginal zone lymphoma (MZL), which has been less studied. Large-scale data with long-term follow-up to investigate MZL transformation is limited. Here, by reporting a US-Nationwide cohort of 30,619 MZL patients diagnosed between 2000 and 2019, we found that transformation occurred in 2.08% (N = 624) of MZL cases, with the transformation incidence of 3.1 per 1,000 person-years. Advanced Ann Arbor stage, nodal MZL (NMZL) and splenic MZL (SMZL) were associated with an elevated risk of transformation. Certain subtype-specific characteristics, such as non-gastric extra-nodal MZL (vs. gastric, HR, 1.51, 95%CI 1.13-2.04; p = 0.006), and receiving splenectomy for SMZL (HR, 2.04, 95%CI 1.28-3.26; p = 0.003), also indicated a higher risk of transformation. Besides, transformation independently increased the overall mortality risk (HR, 1.38, 95%CI 1.24-1.53, p < 0.001), especially the higher lymphoma-caused mortality risk (HR, 3.21, 95%CI 2.81-3.67, p < 0.001). Transformation was also associated with a higher percentage of lymphoma-caused deaths. The post-transformation prognostic analyses demonstrated that female gender and age ≥ 65 years independently affected patients' mortalities. These findings, based on the largest cohort to date, contribute to a better understanding of transformed MZL, and provide valuable reference points for guidelines and patient counseling.
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Nanocrystals (NCs) exposed with high-index facets usually show enhanced electrocatalytic performances. However, it is a great challenge to persevere with high-index facets against their high surface energy during the synthesis. Herein, we successfully synthesize concave hexoctahedral (c-HOH) Pd NCs exposed with 48 high-index {741} facets using a facile one-pot wet-chemical protocol. Control experiments illustrate that l-ascorbic acid plays a critical role in the formation of the c-HOH morphology, acting as both reducing and capping agents. Moreover, we can extend the synthesis for fabricating c-HOH Pd@Pt core-shell NCs by simply introducing a Pt precursor into the reaction solution, attaining remarkably boosted electrocatalysis for methanol electrooxidation reaction (MOR). Integrating the merits of {741} facets, concave structure, and ligand and strain effect of the core-shell structure, c-HOH Pd4@Pt1 core-shell NCs showed an excellent MOR mass activity of 1.18 A mgPGM-1 or 3.60 A mgPt-1, which is 3.80 or 11.61 times higher than that of commercial Pt/C, respectively.
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This work compared the effects of dural puncture epidural (DPE), combined spinal epidural analgesia (CSEA) and epidural analgesia (EA) on labor analgesia for primiparae and their impacts on maternal and infant safety. A total of 204 primiparae in need of labor analgesia for vaginal delivery were allocated to DPE, CSEA and EA groups. At 10 min, 30 min and 1 h after analgesia, the DPE and CSEA groups showed lower VAS scores and quicker onset of action than EA group. There was no significant difference in the duration of analgesia and labor and fetal decelerations among the 3 groups. At 1 min and 5 min after childbirth, the neonatal Apgar scores showed no significant difference between the 3 groups. The Bromage scores of DPE and EA groups were lower than those of CSEA group. The incidence of pruritus, hypotension, and postpartum headache in DPE and EA groups were lower than those in CSEA group. To sum up, the efficacy of DPE in labor analgesia for primiparae is similar to that of CSEA, with no obvious effect on labor stage and neonatal Apgar score, no additional complications and less LLMB, pruritus, hypotension and postpartum headache.
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Analgesia Epidural , Analgesia Obstétrica , Puntaje de Apgar , Trabajo de Parto , Humanos , Femenino , Embarazo , Analgesia Epidural/métodos , Analgesia Epidural/efectos adversos , Adulto , Trabajo de Parto/efectos de los fármacos , Analgesia Obstétrica/métodos , Analgesia Obstétrica/efectos adversos , Recién Nacido , Paridad , Adulto JovenRESUMEN
Sperm, a crucial gamete for reproduction in sexual reproduction, is generated through the proliferation, differentiation, and morphological transformations of spermatogonial stem cells within the specialized microenvironment of the testes. Replicating this environment artificially presents challenges. However, interdisciplinary advancements in physics, materials science, and cell engineering have facilitated the utilization of innovative materials, technologies, and structures for inducing in vitro sperm production. This article offers a comprehensive overview of research progress on inducing in vitro sperm production by categorizing techniques into two major systems based on matrix-based and non-matrix-based approaches, respectively. Detailed discussions are provided for both types of technology systems through comparisons of their similarities and differences, as well as research advancements. The aim is to provide researchers in this field with a comprehensive panoramic view while presenting our own perspectives and prospects.
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Espermatogénesis , Humanos , Masculino , Animales , Diferenciación Celular , Espermatozoides/fisiología , Espermatozoides/citología , Espermatozoides/metabolismo , Testículo/citologíaRESUMEN
Thirteen compounds were isolated and identified from 70% ethanol extract of the roots of Gentiana macrophylla by multi-chromatographic methods, including microporous resin, silica gel, and C_(18) reversed-phase column chromatography, as well as HPLC as follows: macrophylloside G(1), macrophylloside D(2), 5-formyl-2,3-dihydroisocoumarin(3),(+)-medicarpin(4),(+)-syringaresinol(5), liquiritigenin(6),(3R)-sativanone(7),(3R)-3'-O-methylviolanone(8), 4,2',4'-trihydroxychalcone(9), latifolin(10), gentioxepine(11), 6α-hydroxycyclonerolidol(12), and ethyl linoleate(13). Compound 1 was a new benzopyran glycoside. Compounds 4, 6-10, 12, and 13 were isolated for the first time from Gentiana plants. Compounds 1 and 2 showed promising hepatoprotective activity against D-GalN-induced AML12 cell damage at the concentration of 10 µmol·L~(-1), and compound 2 exhibited more significant activity than silybin at the same concentration.
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Glicósidos Cardíacos , Éteres , Gentiana , Gentiana/química , Glicósidos/farmacología , Benzopiranos , GlucósidosRESUMEN
NDV as an attractive candidate for oncolytic immunotherapy selectively lyses tumor cells but shows limited anti-tumor immunity. Immune co-stimulator OX40 ligand (OX40L) boosts anti-tumor immunity response by delivering a potent costimulatory signal to CD4+ and CD8+ T cells. To improve the anti-tumor immunity of NDV, the recombinant NDV expressing the murine OX40L (rNDV-mOX40L) was engineered. The viral growth kinetics was examined in CT26 cell lines. The ability of rNDV-mOX40L to express mOX40L was detected in the infected tumor cells and tumor tissues. The anti-tumor activity of rNDV-mOX40L was studied in the CT26 animal model. Tumor-specific CD4+, CD8+ and OX40+ T cells were examined by immunohistochemistry staining. The virus growth curve showed that the insertion of the mOX40L gene did not affect the growth kinetics of NDV. rNDV-mOX40L expresses mOX40L and effectively inhibits the growth of CT26 colorectal cancer in vivo. The tumor inhibition rate of the rNDV-mOX40L-treated group was increased by 15.8% compared to that of NDV-treated group in the CT26 model. Furthermore, immunohistochemistry staining of tumor tissues removed from the CT26 model revealed that intense infiltration of tumor-specific CD4+, CD8+ T cells, especially OX40+ T cells were found in the rNDV-mOX40L-treated group. FACS showed that rNDV-mOX40L significantly enhanced the number of CD4+ and CD8+ T cells in spleen. Moreover, compared to the NDV-treated group, the level of mouse IFN-γ protein in the tumor site increased significantly in the rNDV-mOX40L-treated group. Taken together, rNDV-mOX40L exhibited superior anti-tumor immunity by stimulating tumor-specific T cells and may be a promising agent for cancer immunotherapy.
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Neoplasias Colorrectales , Virus Oncolíticos , Animales , Ratones , Virus de la Enfermedad de Newcastle/genética , Virus de la Enfermedad de Newcastle/metabolismo , Linfocitos T CD8-positivos , Adyuvantes Inmunológicos/metabolismo , Ligando OX40/genética , Ligando OX40/metabolismo , Virus Oncolíticos/genética , Interleucina-2 , Neoplasias Colorrectales/terapiaRESUMEN
Microbiome samples are accumulating at an unprecedented speed. As a result, a massive amount of samples have become available for the mining of the intrinsic patterns among them. However, due to the lack of advanced computational tools, fast yet accurate comparisons and searches among thousands to millions of samples are still in urgent need. In this work, we proposed the Meta-Prism method for comparing and searching the microbial community structures amongst tens of thousands of samples. Meta-Prism is at least 10 times faster than contemporary methods serving the same purpose and can provide very accurate search results. The method is based on three computational techniques: dual-indexing approach for sample subgrouping, refined scoring function that could scrutinize the minute differences among samples, and parallel computation on CPU or GPU. The superiority of Meta-Prism on speed and accuracy for multiple sample searches is proven based on searching against ten thousand samples derived from both human and environments. Therefore, Meta-Prism could facilitate similarity search and in-depth understanding among massive number of heterogenous samples in the microbiome universe. The codes of Meta-Prism are available at: https://github.com/HUST-NingKang-Lab/metaPrism.
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Metagenómica/métodos , Microbiota , Humanos , Metagenómica/normas , ARN Ribosómico 16S/genética , Sensibilidad y Especificidad , Programas Informáticos/normasRESUMEN
This paper presents a method to measure the three-dimensional distribution of uniaxial stress based on Terahertz Time Domain Spectroscopy (THz-TDS). The measurement principle was first established, which combines the computed tomography (CT) method and the photo-elastic effects. A classic filtered back-projection algorithm is adopted to calculate the three-dimensional stress fields from THz-TDS scanning images. Then, in verification experiment, the uniaxial stress distribution in the compressed cylinder and the stretched screw is obtained based on the measurement principle. Finally, the reliability of the proposed method has been verified by comparing the experiment results with the finite element simulation. A reasonable agreement is obtained.
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BACKGROUND AND AIMS: Hepatic ischaemia/reperfusion injury (HIRI) is a pathophysiological process that occurs during the liver resection and transplantation. Reportedly, peroxisome proliferator-activated receptor ß/δ (PPARß/δ) can ameliorate kidney and myocardial ischaemia/reperfusion injury. However, the effect of PPARß/δ in HIRI remains unclear. METHODS: Mouse hepatic ischaemia/reperfusion (I/R) models were constructed for in vivo study. Primary hepatocytes and Kupffer cells (KCs) isolated from mice and cell anoxia/reoxygenation (A/R) injury model were constructed for in vitro study. Liver injury and inflammation were investigated. Small molecular compounds (GW0742 and GSK0660) and adenoviruses were used to interfere with PPARß/δ. RESULTS: We found that PPARß/δ expression was increased in the I/R and A/R models. Overexpression of PPARß/δ in hepatocytes alleviated A/R-induced cell apoptosis, while knockdown of PPARß/δ in hepatocytes aggravated A/R injury. Activation of PPARß/δ by GW0742 protected against I/R-induced liver damage, inflammation and cell death, whereas inhibition of PPARß/δ by GSK0660 had the opposite effects. Consistent results were obtained in mouse I/R models through the tail vein injection of adenovirus-mediated PPARß/δ overexpression or knockdown vectors. Furthermore, knockdown and overexpression of PPARß/δ in KCs aggravated and ameliorated A/R-induced hepatocyte injury, respectively. Gene ontology and gene set enrichment analysis showed that PPARß/δ deletion was significantly enriched in the NF-κB pathway. PPARß/δ inhibited the expression of p-IKBα and p-P65 and decreased NF-κB activity. CONCLUSIONS: PPARß/δ exerts anti-inflammatory and anti-apoptotic effects on HIRI by inhibiting the NF-κB pathway, and hepatocytes and KCs may play a synergistic role in this phenomenon. Thus, PPARß/δ is a potential therapeutic target for HIRI.
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PPAR delta , PPAR-beta , Daño por Reperfusión , Ratones , Animales , PPAR-beta/genética , PPAR-beta/metabolismo , FN-kappa B/metabolismo , PPAR delta/genética , PPAR delta/metabolismo , Hígado/metabolismo , Tiazoles/farmacología , Inflamación , Modelos Animales de Enfermedad , Daño por Reperfusión/prevención & control , IsquemiaRESUMEN
Solvent accessibility has been extensively used to characterize and predict the chemical properties of the surface residues of soluble proteins. However, there is not yet a widely accepted quantity of the same dimension for the study of lipid-accessible residues of membrane proteins. In this study, we propose that lipid accessibility, defined in a similar way to solvent accessibility, can be used to characterize the lipid-accessible residues of membrane proteins. Moreover, we developed a deep learning-based method, ProtRAP (Protein Relative Accessibility Predictor), to predict the relative lipid accessibility and relative solvent accessibility of residues from a given protein sequence, which can infer which residues are likely accessible to lipids, accessible to solvent, or buried in the protein interior in one run.
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Lípidos , Proteínas de la Membrana , Solventes/química , Proteínas de la Membrana/química , Secuencia de Aminoácidos , Lípidos/químicaRESUMEN
Tyrosinase (TYR), as an important biological enzyme, has been widely used in synthetic biology, medical hairdressing, environmental detection, biological sensors, and other fields. In clinical practice, tyrosinase activity is an important indicator for detecting melanoma. Therefore, the detection of tyrosinase activity is of great importance. Based on the polyphenol oxidase activity of tyrosinase, a simple and rapid detection method was proposed based on the adjustable light scattering properties of cobalt hydroxyl oxide nanoflakes (CoOOH NFs). It was found that the amount and size of CoOOH NFs decreased due to the redox reaction mediated by catechol (CC), resulting in a lower light scattering signal of CoOOH NFs. However, in the presence of tyrosinase, catechol was oxidized to a quinone structure, resulting in the reduced decomposition of CoOOH NFs and recovered light scattering signal, which was developed for the quantitative detection of tyrosinase activity. It was found that in the range of 10-400 U/L, the light scattering intensity was correlated linearly with tyrosinase activity, and the limit of detection was 6.71 U/L (3σ/k). To verify the feasibility of the proposed method in clinical samples, the spiked recovery experiments were carried out with human serum samples, which showed recovery rates between 93.0% and 104.6%, suggesting the high accuracy. The proposed assay provides a simple and rapid method for detection of a natural enzyme based on the adjustable light scattering properties of CoOOH nanoflakes, which lays the foundation for the development of various enzyme sensing applications in the future.
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Monofenol Monooxigenasa , Óxidos , Humanos , Óxidos/química , Cobalto/químicaRESUMEN
OBJECTIVE: Chronic cerebral hypoperfusion (CCH) can cause a series of pathophysiological processes, including neuronal autophagy and apoptosis. VEGF-A has been reported to affect angiogenesis and neurogenesis in many CNS diseases. However, its effects on neuronal autophagy and apoptosis, as well as the underlying mechanisms in CCH remain unclear. METHODS: To address these issues, the CCH model was established by permanent bilateral common carotid artery occlusion (2VO). Rats were sacrificed at different stages of CCH. Hippocampal morphological and ultrastructural changes were detected using HE staining and electron microscopy. The immunoreactivities of microtubule-associated protein 1 light chain 3 (LC3) and phospho-cAMP response element binding protein (p-CREB) were examined by immunofluorescence staining. The neuronal apoptosis was detected via TUNEL staining. The levels of LC3-II, Beclin-1, Akt, p-Akt, CREB, p-CREB, Caspase-3, and Bad were accessed by Western blotting. Furthermore, mouse hippocampal HT22 neurons received the oxygen and glucose deprivation (OGD) treatment, VEGF-A treatment, and GSK690693 (an Akt inhibitor) treatment, respectively. RESULTS: LC3-II protein started to increase at 3 days of CCH, peaked at 4 weeks of CCH, then decreased. CCH increased the levels of LC3-II, Caspase-3, and Bad, and decreased the levels of p-Akt, CREB, and p-CREB, which were reversed by VEGF-A treatment. VEGF-A also improved CCH-induced neuronal ultrastructural injuries and apoptosis in the hippocampus in vitro. In HT22, the anti-apoptosis and pro-phosphorylation of VEGF-A were reversed by GSK690693. CONCLUSION: Present results provide a novel neuroprotective effect of VEGF-A in CCH that is related to the inhibition of neuronal autophagy and activation of the Akt/CREB signaling, suggesting a potential therapeutic strategy for ischemic brain damage.
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Cyanogen chloride (CNCl) is highly toxic and volatile, and it is difficult to effectively remove via porous substances such as activated carbon due to the weak interaction between CNCl and the adsorbent surface. Developing a highly effective elimination material against CNCl is of great importance in military chemical protection. In this work, a new metal-organic framework (MOF) CuBTC@PA-PEI (polyacrylate-polyethyleneimine) composite was prepared and exhibited excellent CNCl elimination performance in the breakthrough tests. PEI was used for the functionalization of PA with amino groups, which is beneficial to anchor with metal ions of MOF. Afterward, the growth of MOF occurred on the surface and in the pores of the matrix by molecular self-assembly via our newly proposed stepwise impregnation layer-by-layer growth method. Breakthrough tests were performed to evaluate the elimination performance of the composites against CNCl. Compared with the pristine CuBTC powder, the CuBTC@PA-PEI composite exhibited better adsorption capacity and a longer breakthrough time. By compounding with the PA matrix, a hierarchically porous structure of CuBTC@PA-PEI composite was constructed, which provides a solution to the mass transfer problem of pure microporous MOF materials. It also solves the problems of MOF molding and lays a foundation for the practical application of MOF.
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Microplastic pollution has gradually become a major global concern, due to the widespread use of plastics. Microplastics enter the environment and are degradated, while also being ingested by organisms, affecting various physiological functions and adversely affecting the health of organisms. Microplastic pollution is currently a wide concern, but data on the impact on organisms is still not sufficient. Therefore, this review summarizes the research on microplastic pollution in marine, soil and fresh water, and its impact on organisms, focusing on the effects of microplastics on organisms' feeding behavior and oxidative stress responses, intestinal microbes and reproductive function, and the combined effects of microplastic pollutants on organisms. We also summarized the various possible ways of microplastics entering into the human body, and posing a potential threat to human health, which still needs further research.
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Microplásticos , Contaminantes Químicos del Agua , Humanos , Microplásticos/toxicidad , Plásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Contaminación Ambiental , EcosistemaRESUMEN
Objective: The aim of our study was to evaluate the effect of tear and repair of the lateral meniscal posterior root (LMPR) on the patellofemoral contact pressure of the knee after anterior cruciate ligament (ACL) reconstructed. Methods: This was a descriptive study. Six fresh-frozen cadaveric knees collected by The Third Hospital of Hebei Medical University from January 2019 and January 2022 were placed on a customized testing rig. Patellofemoral contact pressures were measured at 30°, 60°, and 90° of flexion using pressure-sensitive film inserted between the patella and trochlea. The following knee states were tested: ACL reconstruction and intact lateral meniscus, ACL reconstruction, and LMPR tear, and ACL reconstruction and LMPR repair. Pressure measurements were recorded for each state. Result: In the ACL-reconstructed knee, a tear of the LMPR increased patellofemoral contact pressure at 30° of knee flexion. The repair of the posterior root by transosseous pull-out suture reduced the patellofemoral contact pressure as the status of intact lateral meniscal posterior root at 30° of knee flexion. There was no statistical difference between ACL reconstruction with the intact meniscal root and with the meniscal root tear and with the meniscal root repair at 60° and 90° of knee flexion. Conclusion: The posterior root tear and repair of the lateral meniscus could have an influence on patellofemoral contact stress of the knee after ACL reconstruction at 30° of knee flexion.
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Mimicking the active site and the substrate binding cavity of the enzyme to achieve specificity in catalytic reactions is an essential challenge. Herein, porous coordination cages (PCCs) with intrinsic cavities and tunable metal centers have proved the regulation of reactive oxygen species (ROS) generating pathways as evidenced by multiple photo-induced oxidations. Remarkably, in the presence of the Zn4 -µ4 -O center, PCC converted dioxygen molecules from triplet to singlet excitons, whereas the Ni4 -µ4 -O center promoted the efficient dissociation of electrons and holes to conduct electron transfer towards substrates. Accordingly, the distinct ROS generation behavior of PCC-6-Zn and PCC-6-Ni enables the conversion of O2 to 1 O2 and O2 â - , respectively. In contrast, the Co4 -µ4 -O center combined the 1 O2 and O2 â - together to generate carbonyl radicals, which in turn reacted with the oxygen molecules. Harnessing the three oxygen activation pathways, PCC-6-M (M=Zn/Ni/Co) display specific catalytic activities in thioanisole oxidation (PCC-6-Zn), benzylamine coupling (PCC-6-Ni), and aldehyde autoxidation (PCC-6-Co). This work not only provides fundamental insights into the regulation of ROS generation by a supramolecular catalyst but also demonstrates a rare example of achieving reaction specificity through mimicking natural enzymes by PCCs.
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Metales , Oxígeno , Especies Reactivas de Oxígeno , Metales/química , Oxidación-Reducción , Oxígeno/químicaRESUMEN
Purpose The development of assistive technologies that support people in social interactions has attracted increased attention in HCI. This paper presents a systematic review of studies of Socially Assistive Systems targeted at older adults and people with disabilities. The purpose is threefold: (1) Characterizing related assistive systems with a special focus on the system design, primarily including HCI technologies used and user-involvement approach taken; (2) Examining their ways of system evaluation; (3) Reflecting on insights for future design research. Methods A systematic literature search was conducted using the keywords "social interactions" and "assistive technologies" within the following databases: Scopus, Web of Science, ACM, Science Direct, PubMed, and IEEE Xplore. Results Sixty-five papers met the inclusion criteria and were further analyzed. Our results showed that there were 11 types of HCI technologies that supported social interactions for target users. The most common was cognitive and meaning understanding technologies, often applied with wearable devices for compensating users' sensory loss; 33.85% of studies involved end-users and stakeholders in the design phase; Four types of evaluation methods were identified. The majority of studies adopted laboratory experiments to measure user-system interaction and system validation. Proxy users were used in system evaluation, especially in initial experiments; 42.46% of evaluations were conducted in field settings, primarily including the participants' own homes and institutions. Conclusion We contribute an overview of Socially Assistive Systems that support social interactions for older adults and people with disabilities, as well as illustrate emerging technologies and research opportunities for future work.
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STUDY QUESTION: Is there an efficient and cost-effective detection platform for different genetic conditions about embryos? SUMMARY ANSWER: A multifunctional haplotyping-based preimplantation genetic testing platform was provided for detecting different genetic conditions. WHAT IS KNOWN ALREADY: Genetic disease and chromosomal rearrangement have been known to significantly impact fertility and development. Therefore, preimplantation genetic testing for aneuploidy (PGT-A), monogenic disorders (PGT-M) and structural rearrangements (PGT-SR), a part of ART, has been presented together to minimize the fetal genetic risk and increase pregnancy rate. For patients or their families who are suffering from chromosome abnormality, monogenic disease, unexplained repeated spontaneous abortion or implantation failure, after accepting genetic counseling, they may be suggested to accept detection from more than one PGT platforms about the embryos to avoid some genetic diseases. However, PGT platforms work through different workflows. The high costliness, lack of material and long-time operation of combined PGT platforms limit their application. STUDY DESIGN, SIZE, DURATION: All 188 embryonic samples from 43 families were tested with HaploPGT platform, and most of their genetic abnormalities had been determined by different conventional PGT methods beforehand. Among them, there were 12 families only carrying structural rearrangements (115 embryos) in which 9 families accepted implantation and 5 families had normal labor ART outcomes, 7 families only carrying monogenic diseases (26 embryos) and 3 families carrying both structural rearrangements and monogenic diseases (26 embryos). Twelve monopronucleated zygotes (1PN) samples and 9 suspected triploid samples were collected from 21 families. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Here, we raised a comprehensive PGT method called HaploPGT, combining reduced representation genome sequencing, read-count analysis, B allele frequency and haplotyping analysis, to simultaneously detect different genetic disorders in one single test. MAIN RESULTS AND THE ROLE OF CHANCE: With 80 million reads (80M) genomic data, the proportion of windows (1 million base pairs (Mb)) containing two or more informative single nucleotide polymorphism (SNP) sites was 97.81%, meanwhile the genotyping error rate stabilized at a low level (2.19%). Furthermore, the informative SNPs were equally distributed across the genome, and whole-genomic haplotyping was established. Therefore, 80M was chosen to balance the cost and accuracy in HaploPGT. HaploPGT was able to identify abnormal embryos with triploid, global and partial loss of heterozygosity, and even to distinguish parental origin of copy number variation in mosaic and non-mosaic embryos. Besides, by retrospectively analyzing 188 embryonic samples from 43 families, HaploPGT revealed 100% concordance with the available results obtained from reference methods, including PGT-A, PGT-M, PGT-SR and PGT-HLA. LIMITATIONS, REASON FOR CAUTION: Despite the numerous benefits HaploPGT could bring, it still required additional family members to deduce the parental haplotype for identifying balanced translocation and monogenic mutation in tested embryos. In terms of PGT-SR, the additional family member could be a reference embryo with unbalanced translocation. For PGT-M, a proband was normally required. In both cases, genomic information from grandparents or parental siblings might help for haplotyping theoretically. Another restriction was that haploid, and diploid resulting from the duplication of a haploid, could not be told apart by HaploPGT, but it was able to recognize partial loss of heterozygosity in the embryonic genome. In addition, it should be noted that the location of rearrangement breakpoints and the situation of mutation sites were complicated, which meant that partial genetic disorders might not be completely detected. WIDER IMPLICATIONS OF THE FINDINGS: HaploPGT is an efficient and cost-effective detection platform with high clinical value for detecting genetic status. This platform could promote the application of PGT in ART, to increase pregnancy rate and decrease the birth of children with genetic diseases. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Natural Science Foundation of China (81873478, to L.H.), National Key R&D Program of China (2018YFC1003100, to L.H.), the Natural Science Foundation of Hunan Province (Grant 2022JJ30414, to P.X.), Hunan Provincial Grant for Innovative Province Construction (2019SK4012) and the Scientific Research Foundation of Reproductive and Genetic Hospital of China International Trust & Investment Corporation (CITIC)-Xiangya (YNXM-201910). Haplotyping analysis has been licensed to Basecare Co., Ltd. L.K., Y.M., K.K., D.Z., N.L., J.Z. and R.D. are Basecare Co., Ltd employees. The other authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.
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Diagnóstico Preimplantación , Embarazo , Femenino , Niño , Humanos , Diagnóstico Preimplantación/métodos , Haplotipos , Estudios Retrospectivos , Triploidía , Variaciones en el Número de Copia de ADN , Pruebas Genéticas/métodos , Aneuploidia , Aberraciones CromosómicasRESUMEN
Metallogels have attracted a great deal of interest because of their intriguing properties and applications in chemsensors, batteries, catalysis, and other fields. In this work, a novel ligand bearing terpyridine and hydroxyamine units was designed and synthesized. The ligand selectively gelated with copper ions in water by heating and cooling or sonication. Different physicochemical studies [Fourier transform infrared, ultraviolet-visible (UV-vis), electron paramagnetic resonance (EPR), scanning electron microscopy, X-ray diffraction, and rheology] were conducted to characterize the gels. We show that coordination interaction, π-π interaction, and noncovalent interaction had obvious effects on the properties of the gel. Additionally, a stable radical hydrogel could be obtained by ultrasound treatment, which was accompanied by color variation from green to blue. This was further confirmed by UV-vis and EPR experiments. Furthermore, the copper metallogels were developed as catalysts for the preparation of 1,2,3-triazole derivatives in water at 25 °C. Although various types of catalysts have been investigated, the use of metallogels as catalysts for the click reaction in water has been scarce. This strategy shows the process is simple, affords a high yield, and is "green" and economical.