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1.
Nat Commun ; 15(1): 6397, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080265

RESUMO

DNA base editing technologies predominantly utilize engineered deaminases, limiting their ability to edit thymine and guanine directly. In this study, we successfully achieve base editing of both cytidine and thymine by leveraging the translesion DNA synthesis pathway through the engineering of uracil-DNA glycosylase (UNG). Employing structure-based rational design, exploration of homologous proteins, and mutation screening, we identify a Deinococcus radiodurans UNG mutant capable of effectively editing thymine. When fused with the nickase Cas9, the engineered DrUNG protein facilitates efficient thymine base editing at endogenous sites, achieving editing efficiencies up to 55% without enrichment and exhibiting minimal cellular toxicity. This thymine base editor (TBE) exhibits high editing specificity and significantly restores IDUA enzyme activity in cells derived from patients with Hurler syndrome. TBEs represent efficient, specific, and low-toxicity approaches to base editing with potential applications in treating relevant diseases.


Assuntos
Edição de Genes , Uracila-DNA Glicosidase , Uracila-DNA Glicosidase/metabolismo , Uracila-DNA Glicosidase/genética , Edição de Genes/métodos , Humanos , Engenharia de Proteínas/métodos , DNA/metabolismo , DNA/genética , Timina/metabolismo , Deinococcus/genética , Deinococcus/enzimologia , Deinococcus/metabolismo , Proteína 9 Associada à CRISPR/metabolismo , Proteína 9 Associada à CRISPR/genética , Mutação , Células HEK293 , Sistemas CRISPR-Cas
2.
ACS Appl Mater Interfaces ; 16(30): 40199-40209, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39029113

RESUMO

Silver nanowires (NWs) (AgNWs) have emerged as the most promising conductive materials in flexible optoelectronic devices owing to their excellent photoelectric properties and mechanical flexibility. It is widely acknowledged that the practical application of AgNW networks faces challenges, such as high surface roughness, poor substrate adhesion, and limited stability. Encapsulating AgNW networks with graphene has been recognized as a viable strategy to tackle these issues. However, conventional methods like self-assembly reduction-oxidation or chemical vapor deposition often yield graphene protective layers with inherent defects. Here, we propose a novel one-step hot-pressing method containing ethanol solution that combines the spontaneous transfer and encapsulation process of rGO films onto the surface of the AgNWs network, enabling the preparation of flexible rGO/AgNWs/PET (reduced graphene oxide/silver NWs/polyethylene terephthalate) electrodes. The composite electrode exhibits outstanding photoelectric properties (T ≈ 88%, R ≈ 6 Ω sq-1) and possesses a smooth surface, primarily attributed to the capillary force generated by ethanol evaporation, ensuring the integrity of the rGO delamination process on the original substrate. The capillary force simultaneously promotes the tight encapsulation of rGO and AgNWs, as well as the welding of the AgNWs junction, thereby enhancing the mechanical stability (20,000 bending cycles and 100 cycles of taping tests), thermal stability (∼30 °C and ∼25% humidity for 150 days), and environmental adaptability (100 days of chemical attack) of the electrode. The electrode's practical feasibility has been validated by its exceptional flexibility and cycle stability (95 and 98% retention after 5000 bending cycles and 12,000 s long-term cycles) in flexible electrochromic devices.

3.
Sci Adv ; 10(14): eadj8379, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579008

RESUMO

Magnetic tunnel junctions (MTJs) are the core element of spintronic devices. Currently, the mainstream writing operation of MTJs is based on electric current with high energy dissipation, and it can be notably reduced if an electric field is used instead. In this regard, it is promising for electric field control of MTJ in the multiferroic heterostructure composed of MTJ and ferroelectrics via strain-mediated magnetoelectric coupling. However, there are only reports on MTJs with in-plane anisotropy so far. Here, we investigate electric field control of the resistance state of MgO-based perpendicular MTJs with easy-cone anisotropic free layers through strain-mediated magnetoelectric coupling in multiferroic heterostructures. A remarkable, nonvolatile, and reversible modulation of resistance at room temperature is demonstrated. Through local reciprocal space mapping under different electric fields for Pb(Mg1/3Nb2/3)0.7Ti0.3O3 beneath the MTJ pillar, the modulation mechanism is deduced. Our work represents a crucial step toward electric field control of spintronic devices with non-in-plane magnetic anisotropy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38602127

RESUMO

The development of stealth devices that are compatible with both infrared (IR) and radar systems remains a significant challenge, as the material properties required for effective IR and radar stealth are often contradictory. In this work, based on an IR electrochromic device (IR-ECD), concepts of metamaterial manipulating electromagnetic waves are applied to develop a multifunctional ultrathin metasurface with a low radar cross section (RCS) and variable infrared emissivity. This paper presents a linear-to-linear polarization conversion metasurface (PCM) designed by hollowing the IR-ECD. In this way, the IR-ECD based on polyaniline (PANI) can also modulate the reflection waves in the microwave band without affecting its features in the infrared region. Thus, the proposed metasurface integrates both microwave stealth and variable infrared emissivity through a single layer. The measured results show that a 10 dB RCS reduction is achieved in the band of 8.46-9.5 GHz, and the infrared emissivity can be adjusted from 0.870 to 0.513 in the infrared stealth band of 8-14 µm. Due to the ultrathin thickness (only 0.081λ0 at 9 GHz), low RCS in the X-band, and variable infrared emissivity, the designed multifunctional stealth metasurface has promising applications on military platforms with various surrounding environments.

5.
Sci Adv ; 10(16): eadl4633, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640249

RESUMO

Magnetic tunnel junctions (MTJs) are the core elements of spintronic devices. Now, the mainstream writing operation of MTJs mainly relies on electric current with high energy dissipation, which can be greatly reduced if an electric field is used instead. In this regard, strain-mediated multiferroic heterostructure composed of MTJ and ferroelectrics are promising with the advantages of room temperature and magnetic field-free as already demonstrated by MTJ with in-plane magnetic anisotropy. However, there is no such report on the perpendicular MTJs (p-MTJs), which have been commercialized. Here, we investigate electric-field control of resistance state of MgO-based p-MTJs in multiferroic heterostructures. A remarkable and nonvolatile manipulation of resistance is demonstrated at room temperature without magnetic field assistance. Through various characterizations and micromagnetic simulation, the manipulation mechanism is uncovered. Our work provides an effective avenue for manipulating p-MTJ resistance by electric fields and is notable for high density and ultralow power spintronic devices.

6.
Pest Manag Sci ; 80(8): 3852-3860, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38511626

RESUMO

BACKGROUND: Reproductive diapause serves as a valuable strategy enabling insects to survive unfavorable seasonal conditions. However, forcing insects into diapause when the environment is conducive to their well-being can cause them to miss out on seasonal opportunities for reproduction. This outcome not only reduces insect populations but also minimizes crop losses caused by insect feeding. Therefore, altering the timing of diapause initiation presents a potential strategy for managing pests. In this study, we examined the possible role of the Insulin Receptor 1 (InR1) in controlling reproductive diapause entry in the male cabbage beetle, Colaphellus bowringi. RESULTS: Compared to short-day (SD) conditions, long-day (LD) conditions led to reproductive diapause of C. bowringi males, characterized by arrested gonad development, increased Triglyceride (TG) accumulation, and upregulated expression of diapause protein 1 and genes associated with lipogenesis and stress tolerance. Upon employing RNA interference to knock down InR1 under SD conditions, males destined for reproduction were compelled into diapause, evidenced by arrested gonadal development, accumulation of TG, and elevated expression of diapause-related genes. Intriguingly, despite the common association of the absence of juvenile hormone (JH) with reproductive diapause in females, the knockdown of InR1 in males did not significant affect the expression of JH biosynthesis and JH response gene. CONCLUSION: The study highlight InR1 is a key factor involved in regulating male reproductive diapause in C. bowringi. Consequently, targeting insulin signaling could be a viable approach to perturb diapause timing, offering a promising strategy for managing pests with reproductive diapause capabilities. © 2024 Society of Chemical Industry.


Assuntos
Besouros , Diapausa de Inseto , Receptor de Insulina , Reprodução , Animais , Masculino , Besouros/fisiologia , Besouros/crescimento & desenvolvimento , Besouros/genética , Receptor de Insulina/metabolismo , Receptor de Insulina/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Fotoperíodo , Feminino
7.
J Affect Disord ; 354: 434-442, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508455

RESUMO

BACKGROUND: The association between physical multimorbidity and depression differs by populations. However, no direct inter- or intrapopulation comparison of the association has been conducted. Thus, this study aims to estimate the association in China and the United States and reveal inter- and intrapopulation differences in the association. METHODS: Middle-aged and older adults from the China Health and Retirement Longitudinal Study and the Health and Retirement Study were included. Physical multimorbidity was defined as the simultaneous presence of two or more chronic physical conditions and depressive symptoms was measured by the Center for Epidemiologic Studies Depression Scale. Generalized estimating equation model and stratification multilevel method were the main statistical models. RESULTS: The presence of physical multimorbidity was associated with a higher risk of depression in both China (RR = 1.360 [95 % CI: 1.325-1.395]) and the US (RR = 1.613 [95 % CI: 1.529-1.701]). For individuals at a low risk of multimorbidity, multimorbidity was associated with 47.4 % (95 % CI: 1.377-1.579) and 71.1 % (95 % CI: 1.412-2.074) increases in the likelihood of depression in China and the US. The effect size was smaller for individuals at a moderate or high risk. However, the cross-national differences were greater for those with a high risk of multimorbidity. LIMITATIONS: The self-report measures, attribution bias. CONCLUSIONS: Compared to Chinese adults, the presence of physical multimorbidity led to an additional increase in depressive symptoms for American counterparts. The association was stronger for individuals at a low risk of multimorbidity, but cross-national differences were observed mostly among individuals at a high risk.


Assuntos
Depressão , Multimorbidade , Pessoa de Meia-Idade , Humanos , Idoso , Depressão/epidemiologia , Estudos Longitudinais , Estudos Transversais , Aposentadoria , Doença Crônica , China/epidemiologia
8.
ACS Nano ; 18(14): 10216-10229, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38436241

RESUMO

Substantial advancements have been achieved in the realm of cardiac tissue repair utilizing functional hydrogel materials. Additionally, drug-loaded hydrogels have emerged as a research hotspot for modulating adverse microenvironments and preventing left ventricular remodeling after myocardial infarction (MI), thereby fostering improved reparative outcomes. In this study, diacrylated Pluronic F127 micelles were used as macro-cross-linkers for the hydrogel, and the hydrophobic drug α-tocopherol (α-TOH) was loaded. Through the in situ synthesis of polydopamine (PDA) and the incorporation of conductive components, an injectable and highly compliant antioxidant/conductive composite FPDA hydrogel was constructed. The hydrogel exhibited exceptional stretchability, high toughness, good conductivity, cell affinity, and tissue adhesion. In a rabbit model, the material was surgically implanted onto the myocardial tissue, subsequent to the ligation of the left anterior descending coronary artery. Four weeks postimplantation, there was discernible functional recovery, manifesting as augmented fractional shortening and ejection fraction, alongside reduced infarcted areas. The findings of this investigation underscore the substantial utility of FPDA hydrogels given their proactive capacity to modulate the post-MI infarct microenvironment and thereby enhance the therapeutic outcomes of myocardial infarction.


Assuntos
Hidrogéis , Infarto do Miocárdio , Animais , Coelhos , Hidrogéis/uso terapêutico , alfa-Tocoferol/uso terapêutico , Infarto do Miocárdio/terapia , Miocárdio , Remodelação Ventricular
9.
Int J Equity Health ; 23(1): 22, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321458

RESUMO

BACKGROUND: Together with rapid urbanization, ambient nitrogen dioxide (NO2) exposure has become a growing health threat. However, little is known about the urban-rural disparities in the health implications of short-term NO2 exposure. This study aimed to compare the association between short-term NO2 exposure and hospitalization for cardiovascular disease (CVD) among urban and rural residents in Shandong Province, China. Then, this study further explored the urban-rural disparities in the economic burden attributed to NO2 and the explanation for the disparities. METHODS: Daily hospitalization data were obtained from an electronic medical records dataset covering a population of 5 million. In total, 303,217 hospital admissions for CVD were analyzed. A three-stage time-series analytic approach was used to estimate the county-level association and the attributed economic burden. RESULTS: For every 10-µg/m3 increase in NO2 concentrations, this study observed a significant percentage increase in hospital admissions on the day of exposure of 1.42% (95% CI 0.92 to 1.92%) for CVD. The effect size was slightly higher in urban areas, while the urban-rural difference was not significant. However, a more pronounced displacement phenomenon was found in rural areas, and the economic burden attributed to NO2 was significantly higher in urban areas. At an annual average NO2 concentration of 10 µg/m3, total hospital days and expenses in urban areas were reduced by 81,801 (44,831 to 118,191) days and 60,121 (33,002 to 86,729) thousand CNY, respectively, almost twice as much as in rural areas. Due to disadvantages in socioeconomic status and medical resources, despite similar air pollution levels in the urban and rural areas of our sample sites, the rural population tended to spend less on hospitalization services. CONCLUSIONS: Short-term exposure to ambient NO2 could lead to considerable health impacts in either urban or rural areas of Shandong Province, China. Moreover, urban-rural differences in socioeconomic status and medical resources contributed to the urban-rural disparities in the economic burden attributed to NO2 exposure. The health implications of NO2 exposure are a social problem in addition to an environmental problem. Thus, this study suggests a coordinated intervention system that targets environmental and social inequality factors simultaneously.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doenças Cardiovasculares , Humanos , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio/análise , População Rural , Estresse Financeiro , Poluição do Ar/análise , China/epidemiologia
10.
Arch Gerontol Geriatr ; 118: 105287, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38029545

RESUMO

BACKGROUND: In the era of rapid aging with a rising prevalence of multimorbidity, complex interactions between physical and psychological conditions have challenged the health care system. However, little is known about the association of the accumulation of chronic conditions and disability in activities of daily living with depressive symptoms, especially in developed countries. METHODS: This population-based cohort study used data from the Health and Retirement Study. A total of 22,335 middle-aged and older adults participated in the 2014 (T1), 2016 (T2), and 2018 (T3) waves of the cohort were included. The accumulation of chronic conditions and disability were defined as the number of chronic diseases and the five activities of daily living. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale. A longitudinal mediation model with a cross-lagged panel model was run. As robust check, the models were applied with a longer follow-up period (from 2012 to 2018). Additionally, results were estimated in China. RESULTS: Bidirectional associations have been found among the accumulation of chronic conditions, disability, and depressive symptoms, especially between disability and depression. Disability (T2) mediated 11.11 % and 16.87 % of the association between the accumulation of chronic conditions (T1) and depression (T3) for men and women in the United States. The results were consistent in robust analysis. CONCLUSIONS: This study found that men and women routinely experienced disability and depressive symptoms because of the accumulation of chronic conditions. In terms of depressive symptoms, women were more sensitive to the accumulation of chronic conditions through disability.


Assuntos
Atividades Cotidianas , Depressão , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Depressão/epidemiologia , Atividades Cotidianas/psicologia , Estudos de Coortes , Estudos Longitudinais , Doença Crônica , China/epidemiologia
11.
J Environ Manage ; 350: 119459, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38000269

RESUMO

High energy consumption is the main obstacle of melting/vitrification technology for the disposal of municipal solid waste incineration fly ash (MSWIFA) for industrial applications. To reduce energy consumption and lower operating costs, oxygen enrichment melting was proposed and studied in this work. This research was conducted in a pilot-scale melting furnace, and three melting conditions were compared and discussed. The results showed that 66% of natural gas was saved and the operating cost was reduced by 55% when oxygen enrichment technology was applied to MSWIFA melting. When coal was used as the fuel with the oxygen enrichment melting technology, the operating cost was even lower at 66.39 dollar/ton of fly ash. Because MSWIFA was a Ca-rich material, the relatively high content of Si and Al in the coal fly ash promoted the formation of vitrificated slag, leading to a reduction in the overall pollution toxicity index (OPTI) of MSWIFA by 99.98%. Meanwhile, SO2, HCl, and secondary fly ash were the main pollutants during MSWIFA melting, and when coal was used as the fuel, the emissions of SO2 and HCl could be reduced and the OPTI of secondary fly ash was suppressed. These results suggested that to obtain the lowest operating cost and reduce secondary pollution during MSWIFA melting, the best option consisted of oxygen enrichment technology with coal as the fuel.


Assuntos
Metais Pesados , Eliminação de Resíduos , Cinza de Carvão , Resíduos Sólidos/análise , Gás Natural , Oxigênio , Incineração , Metais Pesados/análise , Carbono , Material Particulado
12.
Heliyon ; 9(12): e22751, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38090009

RESUMO

Prioritizing areas and targets, coordinated with development gaps, is necessary to achieve the sustainable development goals (SDGs) in the face of resource limitations resulting from coronavirus disease 2019 (COVID-19). The SDG interlinkages further exacerbate the difficulty inherent in addressing these goals. However, previous studies failed to consider the indicator interlinkages in the process of aggregate performance assessments and thus cannot identify priorities based on indicator interlinkages and development gaps. This study integrated network analysis and the technique for order of preference by similarity to ideal solution (TOPSIS) method to convert indicator interlinkages into indicator weights and then assessed the aggregate performance of the SDGs. Subsequently, the prioritized provinces and indicators were identified at the subnational level of China based on the aggregate performance of the SDGs, SDG growth rate and indicator interlinkages. The per capita net income of rural residents (2.3.2), the proportion of people living below 50% of the median income (10.2.1), and the under-five mortality rate (3.2.1) were the most contributing indicators to the aggregate performance of the SDGs, while the common challenges dealt with SDG 16, SDG 6, SDG 7 and SDG 12. Moreover, accelerating the development of western provinces would make it possible to overcome the traditional imbalance status, while resource-driven provinces should be paid special attention due to their poor aggregate performance of the SDGs and their lower growth rate. Thus, a coordinating strategy is highly recommended for allocating resources to the priority targets and finally achieving the SDGs.

13.
Materials (Basel) ; 16(21)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37959596

RESUMO

This study aims to address the issues posed by frost damage to concrete structures in cold regions, focusing on reinforcement and repair methods to increase the service life of existing structures instead of costly reconstruction solutions. Due to the limitations of conventional concrete in terms of durability and strength, this research focused on ultra-high-performance concrete (UHPC) by replacing part of the cement with recycled brick powder (RBP) to strengthen ordinary C50 concrete, obtaining UHPC-NC specimens. Mechanical tests investigated the bonding performance of UHPC-NC specimens under various conditions, including interface agents, surface roughness treatments, and freeze-thaw after 0, 50, 100, and 150 cycles with a 30% replacement rate of RBP. Additionally, a multi-factor calculation formula for interface bonding strength was established according to the test data, and the bonding mechanism and model were analyzed through an SEM test. The results indicate that the interface bonding of UHPC-NC specimens decreased during salt freezing compared to hydro-freezing, causing more severe damage. However, the relative index of splitting tensile strength for cement paste specimens showed increases of 14.01% and 14.97%, respectively, compared to specimens without an interface agent. Using an interface agent improved bonding strength and cohesiveness. The UHPC-NC bonding model without an interfacial agent can be characterized using a three-zone model. After applying an interfacial agent, the model can be characterized by a three-zone, three-layer bonding model. Overall, the RBP-UHPC-reinforced C50 for damaged concrete showed excellent interfacial bonding and frost resistance performance.

14.
Comput Biol Med ; 166: 107397, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37804780

RESUMO

Classification and outcome prediction of intracerebral hemorrhage (ICH) is critical for improving the survival rate of patients. Early or delayed neurological deterioration is common in ICH patients, which may lead to changes in the autonomic nervous system (ANS). Therefore, we proposed a new framework for ICH classification and outcome prediction based on skin sympathetic nervous activity (SKNA) signals. A customized measurement device presented in our previous papers was used to collect data. 117 subjects (50 healthy control subjects and 67 ICH patients) were recruited for this study to obtain their 5-min electrocardiogram (ECG) and SKNA signals. We extracted the signal's time-domain, frequency-domain, and nonlinear features and analyzed their differences between healthy control subjects and ICH patients. Subsequently, we established the ICH classification and outcome evaluation model based on the eXtreme Gradient Boosting (XGBoost). In addition, heart rate variability (HRV) as an ANS assessment method was also included as a comparison method in this study. The results showed significant differences in most features of the SKNA signal between healthy control subjects and ICH patients. The ICH patients with good outcomes have a higher change rate and complexity of SKNA signal than those with bad outcomes. In addition, the accuracy of the model for ICH classification and outcome prediction based on the SKNA signal was more than 91% and 83%, respectively. The ICH classification and outcome prediction based on the SKNA signal proved to be a feasible method in this study. Furthermore, the features of change rate and complexity, such as entropy measures, can be used to characterize the difference in SKNA signals of different groups. The method can potentially provide a new tool for rapid classification and outcome prediction of ICH patients. Index Terms-intracerebral hemorrhage (ICH), skin sympathetic nervous activity (SKNA), classification, outcome prediction, cardiovascular and cerebrovascular diseases.

15.
Sci Total Environ ; 904: 166838, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37689206

RESUMO

Arsenic containment is one of the most severe environmental problems. It has been reported that arsenic exposure could cause male reproductive damage. However, the evidence chain from sodium arsenite (NaAsO2) exposure to adverse male fertility outcomes has not been completed by molecular events. In this study, adult male rats were exposed to NaAsO2 for eight weeks via drinking water for verifying their reproductive capacity by checking the phenotypes of testis damage, sperm quality, and female pregnancy rate. H&E staining indicated testicular cells had atrophied, and necrosis was observed under transmission electron microscopy. Sperm viability tended to decrease, and sperm malformation increased. Notably, metabolites in the testes and sperm showed substantial disruption, especially sperm metabolites. The pregnancy rate tests showed that arsenic decreased male rats' reproduction, with some adverse outcomes of the increased numbers of unpregnant females. However, the fetal crown-rump length remained unaltered, indicating that the pregnancy rate was impacted by arsenic exposure but not fetal growth. On arsenic toxicometabolomics analysis, docosahexaenoic acid (DHA) in sperm was the clearest metabolic sign to correlate with the unpregnant rate. In summary, arsenic exposure can cause male infertility via the injured sperm, which results in decreased female pregnancy. The DHA information may imply the dietary intervention for improving sperm quality. Although the fetal growth of the successful pregnancy has not been affected, the changes in epigenetic phenotypes carried by sperms still need to be verified.


Assuntos
Arsênio , Infertilidade Masculina , Gravidez , Humanos , Ratos , Masculino , Feminino , Animais , Testículo/metabolismo , Arsênio/toxicidade , Arsênio/metabolismo , Contagem de Espermatozoides , Sêmen , Ratos Sprague-Dawley , Espermatozoides , Infertilidade Masculina/induzido quimicamente
16.
Chembiochem ; 24(23): e202300582, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37728423

RESUMO

(R)-ß-piperonyl-γ-butyrolactones are key building blocks for the synthesis of podophyllotoxin, which have demonstrated remarkable potential in cancer treatment. Baeyer-Villiger monooxygenases (BVMOs)-mediated asymmetric oxidation is a green approach to produce chiral lactones. While several BVMOs were able to oxidize the corresponding cyclobutanone, most BVMOs gave the (S) enantiomer while Cyclohexanone monooxygenase (CHMO) from Brevibacterium sp. HCU1 gave (R) enantiomer, but with a low enantioselectivity (75 % ee). In this study, we use a strategy called "focused rational iterative site-specific mutagenesis" (FRISM) at residues ranging from 6 Šfrom substrate. The mutations by using a restricted set of rationally chosen amino acids allow the formation of a small mutant library. By generating and screening less than 60 variants, we achieved a high ee of 96.8 %. Coupled with the cofactor regeneration system, 9.3 mM substrate was converted completely in a 100-mL scale reaction. Therefore, our work reveals a promising synthetic method for (R)-ß-piperonyl-γ-butyrolactone with the highest enantioselectivity, and provides a new opportunity for the chem-enzymatic synthesis of podophyllotoxin.


Assuntos
Oxigenases , Podofilotoxina , Oxigenases/metabolismo , Oxigenases de Função Mista/metabolismo , Oxirredução , Especificidade por Substrato
17.
Sensors (Basel) ; 23(15)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37571654

RESUMO

In the clinical treatment of Alzheimer's disease, one of the most important tasks is evaluating its severity for diagnosis and therapy. However, traditional testing methods are deficient, such as their susceptibility to subjective factors, incomplete evaluation, low accuracy, or insufficient granularity, resulting in unreliable evaluation scores. To address these issues, we propose an objective dementia severity scale based on MRI (ODSS-MRI) using contrastive learning to automatically evaluate the neurological function of patients. The approach utilizes a deep learning framework and a contrastive learning strategy to mine relevant information from structural magnetic resonance images to obtain the patient's neurological function level score. Given that the model is driven by the patient's whole brain imaging data, but without any possible biased manual intervention or instruction from the physician or patient, it provides a comprehensive and objective evaluation of the patient's neurological function. We conducted experiments on the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset, and the results showed that the proposed ODSS-MRI was correlated with the stages of AD 88.55% better than all existing methods. This demonstrates its efficacy to describe the neurological function changes of patients during AD progression. It also outperformed traditional psychiatric rating scales in discriminating different stages of AD, which is indicative of its superiority for neurological function evaluation.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Encéfalo
18.
Polymers (Basel) ; 15(12)2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37376285

RESUMO

The application of flexible indium tin oxide (ITO-free) electrochromic devices has steadily attracted widespread attention in wearable devices. Recently, silver nanowire/poly(dimethylsiloxane) (AgNW/PDMS)-based stretchable conductive films have raised great interest as ITO-free substrate for flexible electrochromic devices. However, it is still difficult to achieve high transparency with low resistance due to the weak binding force between AgNW and PDMS with low surface energy because of the possibility of detaching and sliding occurring at the interface. Herein, we propose a method to pattern the pre-cured PDMS (PT-PDMS) by stainless steel film as a template through constructed micron grooves and embedded structure, to prepare a stretchable AgNW/PT-PDMS electrode with high transparency and high conductivity. The stretchable AgNW/PT-PDMS electrode can be stretched (5000 cycles), twisted, and surface friction (3M tape for 500 cycles) without significant loss of conductivity (ΔR/R ≈ 16% and 27%). In addition, with the increase of stretch (stretching to 10-80%), the AgNW/PT-PDMS electrode transmittance increased, and the conductivity increased at first and then decreased. It is possible that the AgNWs in the micron grooves are spread during PDMS stretching, resulting in a larger spreading area and higher transmittance of the AgNWs film; at the same time, the nanowires between the grooves come into contact, thus increasing conductivity. An electrochromic electrode constructed with the stretchable AgNW/PT-PDMS exhibited excellent electrochromic behavior (transmittance contrast from ~61% to ~57%) even after 10,000 bending cycles or 500 stretching cycles, indicating high stability and mechanical robustness. Notably, this method of preparing transparent stretch electrodes based on patterned PDMS provides a promising solution for developing electronic devices with unique structures and high performance.

19.
Front Neurosci ; 17: 1196750, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37255747

RESUMO

Introduction: The function of the autonomic nervous system (ANS) is crucial in the development of intradialytic hypotension (IDH). This study introduced the entropy of heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) to provide a complementary nonlinear and dynamic perspective for evaluating ANS function concerning IDH. Methods: 93 patients undergoing hemodialysis (HD) were enrolled, and the baseline data, electrocardiogram (ECG), and SKNA were collected. The patients were separated into the IDH and nonIDH groups based on the thresholds, which were characterized as reductions in systolic blood pressure (SBP) of at least 20 mm Hg or mean arterial pressure (MAP) of at least 10 mm Hg. We developed a logistic regression model for IDH after analyzing the changes in the time domain, frequency domain, the entropy of HRV, and SKNA indices during HD. Results: After 4-h HD, the detected results for heart rate, the ratio of low frequency and high frequency (LF/HF), and average SKNA (aSKNA) all increased in both groups. Nine out of the ten HRV indices and aSKNA in the nonIDH group were higher than those in the IDH group at most moments. aSKNA was positively correlated with heart rate (p = 0.0001) and LF/HF (p = 0.0005) in the nonIDH group, while the correlation disappeared in the IDH group, which indicated a worse ANS response in IDH patients. The logistic regression model exhibited the results of initial SBP [odds ratio (OR) 1.076; p = 0.001], and the difference between the last and first segments (DLF) of heart rate [OR 1.101; p =0.012] and LF/HF [OR 0.209; p =0.034], as well as the extreme value of the difference between other segments and the first segments (EOF) of aSKNA [OR 2.908; p =0.017], which were independent indicators for IDH. Discussion: The new nonlinear and dynamic assessment perspectives provided by the entropy of HRV and SKNA help to distinguish differences in ANS patterns between IDH patients and nonIDH patients and have the potential to be used in clinical monitoring for HD patients.

20.
Mater Today Bio ; 20: 100626, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37122834

RESUMO

Heart-on-chip emerged as a potential tool for cardiac tissue engineering, recapitulating key physiological cues in cardiac pathophysiology. Controlled electrical stimulation and the ability to provide directly analyzed functional readouts are essential to evaluate the physiology of cardiac tissues in the heart-on-chip platforms. In this scenario, a novel heart-on-chip platform integrating two soft conductive hydrogel pillar electrodes was presented here. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts were seeded into the apparatus to create 3D human cardiac tissues. The application of electrical stimulation improved functional performance by altering the dynamics of tissue structure and contractile development. The contractile forces that cardiac tissues contract was accurately measured through optical tracking of hydrogel pillar displacement. Furthermore, the conductive properties of hydrogel pillars allowed direct and non-invasive electrophysiology studies, enabling continuous monitoring of signal changes in real-time while dynamically administering drugs to the cardiac tissues, as shown by a chronotropic reaction to isoprenaline and verapamil. Overall, the platform for acquiring contractile force and electrophysiological signals in situ allowed monitoring the tissue development trend without interrupting the culture process and could have diverse applications in preclinical drug testing, disease modeling, and therapeutic discovery.

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