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1.
Chembiochem ; : e202400366, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958600

RESUMO

Genetic Code Expansion technology offers significant potential in incorporating noncanonical amino acids into proteins at precise locations, allowing for the modulation of protein structures and functions. However, this technology is often limited by the need for costly and challenging-to-synthesize external noncanonical amino acid sources. In this study, we address this limitation by developing autonomous cells capable of biosynthesizing halogenated tryptophan derivatives and introducing them into proteins using Genetic Code Expansion technology. By utilizing inexpensive halide salts and different halogenases, we successfully achieve the selective biosynthesis of 6-chloro-tryptophan, 7-chloro-tryptophan, 6-bromo-tryptophan, and 7-bromo-tryptophan. These derivatives are introduced at specific positions with corresponding bioorthogonal aminoacyl-tRNA synthetase/tRNA pairs in response to the amber codon. Following optimization, we demonstrate the robust expression of proteins containing halogenated tryptophan residues in cells with the ability to biosynthesize these tryptophan derivatives. This study establishes a versatile platform for engineering proteins with various halogenated tryptophans.

2.
Fish Shellfish Immunol ; 151: 109719, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38914181

RESUMO

Sequestosome 1 (SQSTM1/p62) is a selective autophagy adapter protein that participates in antiviral and bacterial immune responses and plays an important regulatory role in clearing the proteins to be degraded and maintaining intracellular protein homeostasis. In this study, two p62 genes were cloned from common carp (Cyprinus carpio), namely Ccp62-1 and Ccp62-2, and conducted bioinformatics analysis on them. The results showed that Ccp62s had the same structural domain (Phox and Bem1 domain, ZZ-type zinc finger domain, and ubiquitin-associated domain) as p62 from other species. Ccp62s were widely expressed in various tissues of fish, and highly expressed in immune organs such as gills, spleen, head kidney, etc. Subcellular localization study showed that they were mainly distributed in punctate aggregates in the cytoplasm. After stimulation with Aeromonas hydrophila and spring viraemia of carp virus (SVCV), the expression level of Ccp62s was generally up-regulated. Overexpression of Ccp62s in EPC cells could inhibit SVCV replication. Upon A. hydrophila challenge, the bacterial load in Ccp62s-overexpressing group was significantly reduced, the expression levels of pro-inflammatory cytokines and interferon factors were increased, and the survival rate of the fish was improved. These results indicated that Ccp62s were involved in the immune response of common carp to bacterial and viral infections.


Assuntos
Aeromonas hydrophila , Carpas , Doenças dos Peixes , Proteínas de Peixes , Infecções por Bactérias Gram-Negativas , Imunidade Inata , Filogenia , Infecções por Rhabdoviridae , Rhabdoviridae , Animais , Carpas/imunologia , Carpas/genética , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Aeromonas hydrophila/fisiologia , Imunidade Inata/genética , Rhabdoviridae/fisiologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Regulação da Expressão Gênica/imunologia , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/imunologia , Perfilação da Expressão Gênica/veterinária , Alinhamento de Sequência/veterinária , Sequência de Aminoácidos , Autofagia/imunologia
3.
J Am Chem Soc ; 145(38): 21077-21085, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37699243

RESUMO

Covalent organic frameworks (COFs) offer an exceptional platform for constructing membrane nanochannels with tunable pore sizes and tailored functionalities, making them promising candidates for separation, catalysis, and sensing applications. However, the synthesis of COF membranes with highly oriented nanochannels remains challenging, and there is a lack of systematic studies on the influence of postsynthetic modification reactions on functionality distribution along the nanochannels. Herein, we introduced a "prenucleation and slow growth" approach to synthesize a COF membrane featuring highly oriented mesoporous channels and a high Brunauer-Emmett-Teller surface area of 2230 m2 g-1. Functional moieties were anchored to the pore walls via "click" reactions and coordinated with Cu ions to serve as segmentation functions. This led to a remarkable H2/CO2 separation performance that surpassed the Robeson upper bound. Moreover, we found that the functionalities distributed along the nanochannels could be influenced by functionality flexibility and postsynthetic reaction rate. This strategy paved the way for the accurate design and construction of COF-based artificial solid-state nanochannels with high orientation and precisely controlled channel environments.

4.
BMC Pregnancy Childbirth ; 23(1): 805, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990297

RESUMO

OBJECTIVE: To examine family medicine (FM) and obstetrician-gynecologist (OB/GYN) residents' experiences with CenteringPregnancy (CP) group prenatal care (GPNC) as a correlate to perceived likelihood of implementing CP in future practice, as well as knowledge, level of support, and perceived barriers to implementation. METHODS: We conducted a repeated cross-sectional study annually from 2017 to 2019 with FM and OB/GYN residents from residency programs in the United States licensed to operate CP. We applied adjusted logistic regression models to identify predictors of intentions to engage with CP in future practice. RESULTS: Of 212 FM and 176 OB/GYN residents included in analysis, 67.01% of respondents intended to participate as a facilitator in CP in future practice and 51.80% of respondents were willing to talk to decision makers about establishing CP. Both FM and OB/GYN residents who spent more than 15 h engaged with CP and who expressed support towards CP were more likely to participate as a facilitator. FM residents who received residency-based training on CP and who were more familiar with CP reported higher intention to participate as a facilitator, while OB/GYN residents who had higher levels of engagement with CP were more likely to report an intention to participate as a facilitator. CONCLUSION: Engagement with and support towards CP during residency are key factors in residents' intention to practice CP in the future. To encourage future adoption of CP among residents, consider maximizing resident engagement with the model in hours of exposure and level of engagement, including hosting residency-based trainings on CP for FM residents.


Assuntos
Ginecologia , Internato e Residência , Obstetrícia , Feminino , Gravidez , Humanos , Estados Unidos , Ginecologia/educação , Cuidado Pré-Natal , Medicina de Família e Comunidade , Estudos Transversais , Obstetrícia/educação , Inquéritos e Questionários
5.
J Med Internet Res ; 25: e47225, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37267022

RESUMO

BACKGROUND: Social media platforms have been increasingly used to express suicidal thoughts, feelings, and acts, raising public concerns over time. A large body of literature has explored the suicide risks identified by people's expressions on social media. However, there is not enough evidence to conclude that social media provides public surveillance for suicide without aligning suicide risks detected on social media with actual suicidal behaviors. Corroborating this alignment is a crucial foundation for suicide prevention and intervention through social media and for estimating and predicting suicide in countries with no reliable suicide statistics. OBJECTIVE: This study aimed to corroborate whether the suicide risks identified on social media align with actual suicidal behaviors. This aim was achieved by tracking suicide risks detected by 62 million tweets posted in Japan over a 10-year period and assessing the locational and temporal alignment of such suicide risks with actual suicide behaviors recorded in national suicide statistics. METHODS: This study used a human-in-the-loop approach to identify suicide-risk tweets posted in Japan from January 2013 to December 2022. This approach involved keyword-filtered data mining, data scanning by human efforts, and data refinement via an advanced natural language processing model termed Bidirectional Encoder Representations from Transformers. The tweet-identified suicide risks were then compared with actual suicide records in both temporal and spatial dimensions to validate if they were statistically correlated. RESULTS: Twitter-identified suicide risks and actual suicide records were temporally correlated by month in the 10 years from 2013 to 2022 (correlation coefficient=0.533; P<.001); this correlation coefficient is higher at 0.652 when we advanced the Twitter-identified suicide risks 1 month earlier to compare with the actual suicide records. These 2 indicators were also spatially correlated by city with a correlation coefficient of 0.699 (P<.001) for the 10-year period. Among the 267 cities with the top quintile of suicide risks identified from both tweets and actual suicide records, 73.5% (n=196) of cities overlapped. In addition, Twitter-identified suicide risks were at a relatively lower level after midnight compared to a higher level in the afternoon, as well as a higher level on Sundays and Saturdays compared to weekdays. CONCLUSIONS: Social media platforms provide an anonymous space where people express their suicidal thoughts, ideation, and acts. Such expressions can serve as an alternative source to estimating and predicting suicide in countries without reliable suicide statistics. It can also provide real-time tracking of suicide risks, serving as an early warning for suicide. The identification of areas where suicide risks are highly concentrated is crucial for location-based mental health planning, enabling suicide prevention and intervention through social media in a spatially and temporally explicit manner.


Assuntos
Aprendizado Profundo , Mídias Sociais , Suicídio , Humanos , Japão , Fatores de Tempo , Suicídio/psicologia
6.
Int J Appl Earth Obs Geoinf ; 116: 103160, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36570490

RESUMO

Globally, the COVID-19 pandemic has induced a mental health crisis. Social media data offer a unique opportunity to track the mental health signals of a given population and quantify their negativity towards COVID-19. To date, however, we know little about how negative sentiments differ across countries and how these relate to the shifting policy landscape experienced through the pandemic. Using 2.1 billion individual-level geotagged tweets posted between 1 February 2020 and 31 March 2021, we track, monitor and map the shifts in negativity across 217 countries and unpack its relationship with COVID-19 policies. Findings reveal that there are important geographic, demographic, and socioeconomic disparities of negativity across continents, different levels of a nation's income, population density, and the level of COVID-19 infection. Countries with more stringent policies were associated with lower levels of negativity, a relationship that weakened in later phases of the pandemic. This study provides the first global and multilingual evaluation of the public's real-time mental health signals to COVID-19 at a large spatial and temporal scale. We offer an empirical framework to monitor mental health signals globally, helping international authorizations, including the United Nations and World Health Organization, to design smart country-specific mental health initiatives in response to the ongoing pandemic and future public emergencies.

7.
Zhonghua Nan Ke Xue ; 29(1): 66-70, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-37846835

RESUMO

OBJECTIVE: To investigate the clinical effect of pelvic floor muscle rehabilitation training combined with psychological nursing intervention in the treatment of intractable type ⅢB prostatitis. METHODS: We retrospectively analyzed the clinical data on 51 cases of intractable type ⅢB prostatitis treated from October 2020 to October 2022, which were randomly assigned to receive Tamsulosin medication (the control group, n = 24) or pelvic floor muscle rehabilitation training and psychological nursing in addition (the intervention group, n = 27), all for 8 weeks. We obtained NIH-CPSI, IIEF-5, Self-Rating Anxiety Scale (SAS) scores, Self-Rating Depression Scale (SDS) scores, the level of lecithin and the count of leukocytes in the prostatic fluid and the incidence of adverse events, and compared them between the two groups of patients before and after treatment. RESULTS: The total effectiveness rate was significantly higher in the intervention than in the control group (88.9% vs 62.5%, P < 0.05). Compared with the baseline, the NIH-CPSI, IIEF-5, SAS and SDS scores and the lecithin level were remarkably increased in both groups after treatment (P < 0.05), even more significantly in the intervention group than in the control (P < 0.05). No statistically significant difference was observed in the count of leukocytes before and after treatment (P > 0.05). CONCLUSION: On the basis of Tamsulosin medication, the application of pelvic floor rehabilitation training combined with psychological care can significantly enhance the therapeutic effect on type IIIB prostatitis, effectively relieve prostatitis pain, improve erectile function, lessen anxiety and depression symptoms, increase the level of lecithosomes and promote the recovery of prostatic function.


Assuntos
Prostatite , Masculino , Humanos , Prostatite/tratamento farmacológico , Prostatite/complicações , Tansulosina/uso terapêutico , Diafragma da Pelve , Lecitinas , Estudos Retrospectivos , Dor Pélvica/terapia , Doença Crônica
8.
Exp Cell Res ; 405(2): 112678, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34171351

RESUMO

Tumor cell apoptosis evasion is one of the main reasons for easy metastasis occurrence, chemotherapy resistance, and the low five-year survival rate of digestive system tumors. Current research has shown that non-apoptotic cell death plays an important role in tumors of the digestive system. Therefore, increasing the proportion of non-apoptotic tumor cells is one of the effective methods of improving therapeutic efficacies for digestive system tumors. Non-apoptotic cell death modes mainly include autophagic cell death, pyroptosis, ferroptosis, in addition to other cell death modes. This review covers a systematic review relating to the research progress made into autophagic cell death, pyroptosis, ferroptosis, and other cell death modes in the treatment of digestive system tumors. It also highlights how treatment is a reasonable prospect based on clinical experience and provides reliable guidance for the further development of digestive system tumor treatments.


Assuntos
Morte Celular/efeitos dos fármacos , Neoplasias do Sistema Digestório/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Gastrointestinais/tratamento farmacológico , Animais , Autofagia/efeitos dos fármacos , Neoplasias do Sistema Digestório/metabolismo , Neoplasias Gastrointestinais/metabolismo , Humanos , Piroptose/efeitos dos fármacos
9.
Int J Appl Earth Obs Geoinf ; 113: 102967, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36035895

RESUMO

Social media platforms allow users worldwide to create and share information, forging vast sensing networks that allow information on certain topics to be collected, stored, mined, and analyzed in a rapid manner. During the COVID-19 pandemic, extensive social media mining efforts have been undertaken to tackle COVID-19 challenges from various perspectives. This review summarizes the progress of social media data mining studies in the COVID-19 contexts and categorizes them into six major domains, including early warning and detection, human mobility monitoring, communication and information conveying, public attitudes and emotions, infodemic and misinformation, and hatred and violence. We further document essential features of publicly available COVID-19 related social media data archives that will benefit research communities in conducting replicable and reproducible studies. In addition, we discuss seven challenges in social media analytics associated with their potential impacts on derived COVID-19 findings, followed by our visions for the possible paths forward in regard to social media-based COVID-19 investigations. This review serves as a valuable reference that recaps social media mining efforts in COVID-19 related studies and provides future directions along which the information harnessed from social media can be used to address public health emergencies.

10.
Am J Physiol Renal Physiol ; 320(3): F262-F272, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356954

RESUMO

Mitochondrial damage in renal tubular epithelial cells (RTECs) is a hallmark of endotoxin-induced acute kidney injury (AKI). Forkhead box O1 (FOXO1) is responsible for regulating mitochondrial function and is involved in several kidney diseases. Here, we investigated the effect of FOXO1 on endotoxin-induced AKI and the related mechanism. In vivo, FOXO1 downregulation in mouse RTECs and mitochondrial damage were found in endotoxin-induced AKI. Overexpression of FOXO1 by kidney focal adeno-associated virus (AAV) delivery improved renal function and reduced mitochondrial damage. Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1-α), a master regulator of mitochondrial biogenesis and function, was reduced in endotoxin-induced AKI, but the reduction was reversed by FOXO1 overexpression. In vitro, exposure to LPS led to a decline in HK-2 cell viability, mitochondrial fragmentation, and mitochondrial superoxide accumulation, as well as downregulation of FOXO1, PGC1-α, and mitochondrial complex I/V. Moreover, overexpression of FOXO1 in HK-2 cells increased HK-2 cell viability and PGC1-α expression, and it alleviated the mitochondrial injury and superoxide accumulation induced by LPS. Meanwhile, inhibition of FOXO1 in HK-2 cells by siRNA treatment decreased PGC1-α expression and HK-2 cell viability. Chromatin immunoprecipitation assays and PCR analysis confirmed that FOXO1 bound to the PGC1-α promoter in HK-2 cells. In conclusion, downregulation of FOXO1 in RTECs mediated endotoxin-induced AKI and mitochondrial damage. Overexpression of FOXO1 could improve renal injury and mitochondrial dysfunction, and this effect occurred at least in part as a result of PGC1-α signaling. FOXO1 might be a potential target for the prevention and treatment of endotoxin-induced AKI.


Assuntos
Injúria Renal Aguda/metabolismo , Endotoxemia/complicações , Células Epiteliais/metabolismo , Proteína Forkhead Box O1/metabolismo , Túbulos Renais/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Endotoxemia/induzido quimicamente , Células Epiteliais/ultraestrutura , Proteína Forkhead Box O1/genética , Humanos , Túbulos Renais/ultraestrutura , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais
11.
BMC Med ; 19(1): 308, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34872559

RESUMO

BACKGROUND: From 2 January to 14 February 2021, a local outbreak of COVID-19 occurred in Shijiazhuang, the capital city of Hebei Province, with a population of 10 million. We analyzed the characteristics of the local outbreak of COVID-19 in Shijiazhuang and evaluated the effects of serial interventions. METHODS: Publicly available data, which included age, sex, date of diagnosis, and other patient information, were used to analyze the epidemiological characteristics of the COVID-19 outbreak in Shijiazhuang. The maximum likelihood method and Hamiltonian Monte Carlo method were used to estimate the serial interval and incubation period, respectively. The impact of incubation period and different interventions were simulated using a well-fitted SEIR+q model. RESULTS: From 2 January to 14 February 2021, there were 869 patients with symptomatic COVID-19 in Shijiazhuang, and most cases (89.6%) were confirmed before 20 January. Overall, 40.2% of the cases were male, 16.3% were aged 0 to 19 years, and 21.9% were initially diagnosed as asymptomatic but then became symptomatic. The estimated incubation period was 11.6 days (95% CI 10.6, 12.7 days) and the estimated serial interval was 6.6 days (0.025th, 0.975th: 0.6, 20.0 days). The results of the SEIR+q model indicated that a longer incubation period led to a longer epidemic period. If the comprehensive quarantine measures were reduced by 10%, then the nucleic acid testing would need to increase by 20% or more to minimize the cumulative number of cases. CONCLUSIONS: Incubation period was longer than serial interval suggested that more secondary transmission may occur before symptoms onset. The long incubation period made it necessary to extend the isolation period to control the outbreak. Timely contact tracing and implementation of a centralized quarantine quickly contained this epidemic in Shijiazhuang. Large-scale nucleic acid testing also helped to identify cases and reduce virus transmission.


Assuntos
COVID-19 , Período de Incubação de Doenças Infecciosas , Quarentena , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , SARS-CoV-2 , Adulto Jovem
12.
J Transl Med ; 19(1): 391, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526059

RESUMO

BACKGROUND: EMT is an important biological process in the mechanism of tumor invasion and metastasis. However, there are still many unknowns about the specific mechanism of EMT in tumor. At present, a comprehensive analysis of EMT-related genes in colorectal cancer (CRC) is still lacking. METHODS: All the data were downloaded from public databases including TCGA database (488 tumor samples and 52 normal samples) as the training set and the GEO database (GSE40967 including 566 tumor samples and 19 normal samples, GSE12945 including 62 tumor samples, GSE17536 including 177 tumor samples, GSE17537 including 55 tumor samples) as the validation sets. One hundred and sixty-six EMT-related genes (EMT-RDGs) were selected from the Molecular Signatures Database. Bioinformatics methods were used to analyze the correlation between EMT-RDGs and CRC prognosis, metastasis, drug efficacy, and immunity. RESULTS: We finally obtained nine prognostic-related EMT-RDGs (FGF8, NOG, PHLDB2, SIX2, SNAI1, TBX5, TIAM1, TWIST1, TCF15) through differential expression analysis, Unicox and Lasso regression analysis, and then constructed a risk prognosis model. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high-risk and low-risk groups and the different states of the nine prognostic-related EMT-RDGs. The methylation level and mutation status of nine prognostic-related EMT-RDGs all affect their regulation of EMT. The Cox proportional hazards regression model was also constructed by the methylation sites of nine prognostic-related EMT-RDGs. In addition, the expression of FGF8, PHLDB2, SIX2, and SNAIL was higher and the expression level of NOG and TWIST1 was lower in the non-metastasis CRC group. Nine prognostic-related EMT-RDGs also affected the drug treatment response of CRC. CONCLUSIONS: Targeting these nine prognostic-related EMT-RDGs can regulate CRC metastasis and immune, which is beneficial for the prognosis of CRC patients, improve drug sensitivity in CRC patients.


Assuntos
Neoplasias Colorretais , Preparações Farmacêuticas , RNA Longo não Codificante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico
13.
J Med Internet Res ; 23(9): e30854, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34346888

RESUMO

BACKGROUND: The COVID-19 pandemic has imposed a large, initially uncontrollable, public health crisis both in the United States and across the world, with experts looking to vaccines as the ultimate mechanism of defense. The development and deployment of COVID-19 vaccines have been rapidly advancing via global efforts. Hence, it is crucial for governments, public health officials, and policy makers to understand public attitudes and opinions towards vaccines, such that effective interventions and educational campaigns can be designed to promote vaccine acceptance. OBJECTIVE: The aim of this study was to investigate public opinion and perception on COVID-19 vaccines in the United States. We investigated the spatiotemporal trends of public sentiment and emotion towards COVID-19 vaccines and analyzed how such trends relate to popular topics found on Twitter. METHODS: We collected over 300,000 geotagged tweets in the United States from March 1, 2020 to February 28, 2021. We examined the spatiotemporal patterns of public sentiment and emotion over time at both national and state scales and identified 3 phases along the pandemic timeline with sharp changes in public sentiment and emotion. Using sentiment analysis, emotion analysis (with cloud mapping of keywords), and topic modeling, we further identified 11 key events and major topics as the potential drivers to such changes. RESULTS: An increasing trend in positive sentiment in conjunction with a decrease in negative sentiment were generally observed in most states, reflecting the rising confidence and anticipation of the public towards vaccines. The overall tendency of the 8 types of emotion implies that the public trusts and anticipates the vaccine. This is accompanied by a mixture of fear, sadness, and anger. Critical social or international events or announcements by political leaders and authorities may have potential impacts on public opinion towards vaccines. These factors help identify underlying themes and validate insights from the analysis. CONCLUSIONS: The analyses of near real-time social media big data benefit public health authorities by enabling them to monitor public attitudes and opinions towards vaccine-related information in a geo-aware manner, address the concerns of vaccine skeptics, and promote the confidence that individuals within a certain region or community have towards vaccines.


Assuntos
COVID-19 , Mídias Sociais , Vacinas contra COVID-19 , Humanos , Pandemias , Opinião Pública , SARS-CoV-2 , Estados Unidos
14.
Angew Chem Int Ed Engl ; 60(39): 21304-21309, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34041828

RESUMO

Coordination polymer (CP) glasses offer a way to tackle the fabrication challenges encountered by inorganic porous membranes and show great potentials for size-exclusive gas separation. However, their processability and performance still cannot simultaneously meet the requirements for high-performance membrane separation. Herein, we have developed a series of CP glasses (M-P-dmbIm, M=Zn, Cd, Cu, and Mn), which possess low vitrification temperature as well as low viscosity (η) and lave capability above the transition temperatures. The derived glass (ag M-P-dmbIm) membranes show outstanding performances for H2 /CO2 , H2 /N2 , and H2 /CH4 separation, which all far surpass the Robeson upper bound and even rival against the best of the state-of-the-art gas separation membranes. The low viscosities not only allow us to hot-cast or hot-press the CP glasses into thin membranes within 5 min without sacrificing their selectivity and permeability, but also endow the resulted glass membranes with healing ability.

15.
J Am Chem Soc ; 142(30): 13180-13189, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32619351

RESUMO

Synthesis of bridged scaffolds via Type II cyclization constitutes substantial challenges due to the intrinsic ring strain accumulated in reaction transition states. Catalytic enantioselective Type II-cyclization methods are even rarer. Here, we describe a detailed study of developing a Rh(I)-catalyzed enantioselective intramolecular Type II cyclization of alkynes via C-C activation of cyclobutanones. This method offers a rapid approach to access a wide range of functionalized [3.3.1]-bridged bicycles along with an exocyclic olefin and an all-carbon quaternary stereocenter. Excellent enantioselectivity has been achieved using a combination of cationic rhodium(I) and DTBM-segphos. Attributed to the redox neutral and strong acid/base-free reaction conditions, high chemoselectivity has also been observed. For the oxygen-tethered substrates, the reaction can proceed at room temperature. In addition, partial kinetic resolution has been achieved for substrates with existing stereocenters, forging interesting chiral tricyclic scaffolds. The methylalkyne-derived substrates gave unexpected dimeric structures in good yield with excellent enantioselectivity and complete diastereoselectivity. Furthermore, the bridged bicyclic products can be diversely functionalized through simple transformations. Finally, mechanistic studies reveal a surprising reaction pathway that involves forming a metal-stabilized anti-Bredt olefin intermediate.


Assuntos
Alcinos/química , Compostos Bicíclicos com Pontes/síntese química , Ciclobutanos/síntese química , Compostos Bicíclicos com Pontes/química , Reação de Cicloadição , Ciclobutanos/química , Conformação Molecular , Estereoisomerismo
16.
J Xray Sci Technol ; 28(6): 1091-1111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33044223

RESUMO

BACKGROUND: Radiation risk from computed tomography (CT) is always an issue for patients, especially those in clinical conditions in which repeated CT scanning is required. For patients undergoing repeated CT scanning, a low-dose protocol, such as sparse scanning, is often used, and consequently, an advanced reconstruction algorithm is also needed. OBJECTIVE: To develop a novel algorithm used for sparse-view CT reconstruction associated with the prior image. METHODS: A low-dose CT reconstruction method based on prior information of normal-dose image (PI-NDI) involving a transformed model for attenuation coefficients of the object to be reconstructed and prior information application in the forward-projection process was used to reconstruct CT images from sparse-view projection data. A digital extended cardiac-torso (XCAT) ventral phantom and a diagnostic head phantom were employed to evaluate the performance of the proposed PI-NDI method. The root-mean-square error (RMSE), peak signal-to-noise ratio (PSNR) and mean percent absolute error (MPAE) of the reconstructed images were measured for quantitative evaluation of the proposed PI-NDI method. RESULTS: The reconstructed images with sparse-view projection data via the proposed PI-NDI method have higher quality by visual inspection than that via the compared methods. In terms of quantitative evaluations, the RMSE measured on the images reconstructed by the PI-NDI method with sparse projection data is comparable to that by MLEM-TV, PWLS-TV and PWLS-PICCS with fully sampled projection data. When the projection data are very sparse, images reconstructed by the PI-NDI method have higher PSNR values and lower MPAE values than those from the compared algorithms. CONCLUSIONS: This study presents a new low-dose CT reconstruction method based on prior information of normal-dose image (PI-NDI) for sparse-view CT image reconstruction. The experimental results validate that the new method has superior performance over other state-of-art methods.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Cabeça/diagnóstico por imagem , Humanos , Imagens de Fantasmas , Razão Sinal-Ruído
17.
J Xray Sci Technol ; 28(3): 541-553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176675

RESUMO

PURPOSE: Segmentation of magnetic resonance images (MRI) of the left ventricle (LV) plays a key role in quantifying the volumetric functions of the heart, such as the area, volume, and ejection fraction. Traditionally, LV segmentation is performed manually by experienced experts, which is both time-consuming and prone to subjective bias. This study aims to develop a novel capsule-based automated segmentation method to automatically segment the LV from images obtained by cardiac MRI. METHOD: The technique applied for segmentation uses Fourier analysis and the circular Hough transform (CHT) to indicate the approximate location of the LV and a network capsule to precisely segment the LV. The neurons of the capsule network output a vector and preserve much of the information about the input by replacing the largest pooling layer with convolutional strides and dynamic routing. Finally, the segmentation result is postprocessed by threshold segmentation and morphological processing to increase the accuracy of LV segmentation. RESULTS: We fully exploit the capsule network to achieve the segmentation goal and combine LV detection and capsule concepts to complete LV segmentation. In the experiments, the tested methods achieved LV Dice scores of 0.922±0.05 end-diastolic (ED) and 0.898±0.11 end-systolic (ES) on the ACDC 2017 data set. The experimental results confirm that the algorithm can effectively perform LV segmentation from a cardiac magnetic resonance image. To verify the performance of the proposed method, visual and quantitative comparisons are also performed, which show that the proposed method exhibits improved segmentation accuracy compared with the traditional method. CONCLUSIONS: The evaluation metrics of medical image segmentation indicate that the proposed method in combination with postprocessing and feature detection effectively improves segmentation accuracy for cardiac MRI. To the best of our knowledge, this study is the first to use a deep learning model based on capsule networks to systematically evaluate end-to-end LV segmentation.


Assuntos
Aprendizado Profundo , Ventrículos do Coração/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Humanos
18.
Angew Chem Int Ed Engl ; 59(20): 7848-7856, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32086872

RESUMO

To show the synthetic utility of the catalytic C-C activation of less strained substrates, described here are the collective and concise syntheses of the natural products (-)-microthecaline A, (-)-leubehanol, (+)-pseudopteroxazole, (+)-seco-pseudopteroxazole, pseudopterosin A-F and G-J aglycones, and (+)-heritonin. The key step in these syntheses involve a Rh-catalyzed C-C/C-H activation cascade of 3-arylcyclopentanones, which provides a rapid and enantioselective route to access the polysubstituted tetrahydronaphthalene cores presented in these natural products. Other important features include 1) the direct C-H amination of the tetralone substrate in the synthesis of (-)-microthecaline A, 2) the use of phosphoric acid to enhance efficiency and regioselectivity for problematic cyclopentanone substrates in the C-C activation reactions, and 3) the direct conversion of serrulatane into amphilectane diterpenes by an allylic cyclodehydrogenation coupling.


Assuntos
Ciclopentanos/química , Sesquiterpenos/química , Sesquiterpenos/síntese química , Aminação , Catálise , Técnicas de Química Sintética , Hidrogenação , Ródio/química
19.
Angew Chem Int Ed Engl ; 59(11): 4401-4405, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-31849167

RESUMO

Commercial ultrafiltration membranes have proliferated globally for water treatment. However, their pore sizes are too large to sieve gases. Conjugated microporous polymers (CMPs) feature well-developed microporosity yet are difficult to be fabricated into membranes. Herein, we report a strategy to prepare molecular-sieving membranes by partitioning the mesoscopic channels in water ultrafiltration membrane (PSU) into ultra-micropores by space-confined polymerization of multi-functionalized rigid building units. Nine CMP@PSU membranes were obtained, and their separation performance for H2 /CO2 , H2 /N2 , and H2 /CH4 pairs surpass the Robeson upper bound and rival against the best of those reported membranes. Furthermore, highly crosslinked skeletons inside the channels result in the structural robustness and transfer into the excellent aging resistance of the CMP@PSU. This strategy may shed light on the design and fabrication of high-performance polymeric gas separation membranes.

20.
Am J Physiol Renal Physiol ; 317(5): F1311-F1317, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31339772

RESUMO

Ischemia-reperfusion (I/R)-induced acute kidney injury (I/R-AKI) favors mitochondrial permeability transition pore (mPTP) opening and subsequent cell death. Cyclophilin D (CypD) is an essential component of the mPTP, and recent findings have implicated the p53-CypD complex in cell death. To evaluate the role of p53-CypD after I/R-AKI, we tested the hypothesis that the p53-CypD complex mediates renal tubular cell apoptosis in I/R-AKI via mPTP opening. Expression of p53 and cleaved caspase-3 was significantly increased in rats subjected to I/R-AKI compared with normal controls and sham-operated controls. The underlying mechanisms were determined using an in vitro model of ATP depletion. Inhibition of mPTP opening using the CypD inhibitor cyclosporin A or siRNA for p53 in ATP-depleted HK-2 cells prevented mitochondrial membrane depolarization and reduced apoptosis. Furthermore, p53 bound to CypD in ATP-depleted HK-2 cells. These results suggest that the p53-CypD complex mediates renal tubular cell apoptosis in I/R-AKI via mPTP opening.


Assuntos
Injúria Renal Aguda/etiologia , Túbulos Renais/citologia , Peptidil-Prolil Isomerase F/metabolismo , Traumatismo por Reperfusão , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose , Linhagem Celular , Células Cultivadas , Ciclosporina/farmacologia , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
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