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Fibers of liquid crystal elastomers (LCEs) as promising artificial muscle show ultralarge and reversible contractile strokes. However, the contractile force is limited by the poor mechanical properties of the LCE fibers. Herein, we report high-strength LCE fibers by introducing a secondary network into the single-network LCE. The double-network LCE (DNLCE) shows considerable improvements in tensile strength (313.9%) and maximum actuation stress (342.8%) compared to pristine LCE. To facilitate the controllability and application, a coiled artificial muscle fiber consisting of DNLCE-coated carbon nanotube (CNT) fiber is prepared. When electrothermally driven, the artificial muscle fiber outputs a high actuation performance and programmable actuation. Furthermore, by knitting the artificial muscle fibers into origami structures, an intelligent gripper and crawling inchworm robot have been demonstrated. These demonstrations provide promising application scenarios for advanced intelligent systems in the future.
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BACKGROUND: The Triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in the risk of ischemic stroke. However, the interplay between TyG levels, lifestyle factors, and their collective impact on stroke risk in non-diabetic populations remains inadequately explored. This study aims to evaluate the association of ischemic stroke with the joint development of the TyG index and lifestyle in the non-diabetic population. METHODS: In this prospective cohort study, data was collected across three consecutive biennial surveys of the Kailuan Study from 2006 to 2011. The dual-trajectory model was used to determine the temporal development of TyG levels and lifestyle scores. Statistical analysis involved Cox regression models to evaluate the association between TyG-lifestyle trajectories and ischemic stroke risk, adjusting for potential confounders. RESULTS: A total of 44,403 participants were included, with five distinct TyG levels and lifestyle scores trajectory subtypes identified. In the multivariable-adjusted analyses, significant differences in ischemic stroke risk among the trajectory subtypes. Group 5, characterized by the highest TyG levels and moderate lifestyle scores, exhibited the greatest ischemic stroke risk (HR = 1.81, 95% CI: 1.51-2.18), while group 4, with moderate TyG levels and higher lifestyle scores, demonstrated the lowest risk (HR = 1.19, 95% CI: 1.04-1.37), compared with group 3. Participants with elevated TyG levels were at an increased risk of ischemic stroke in cases of pronounced insulin resistance, even with a healthy lifestyle. CONCLUSIONS: This study reveals the significant associations between the identified TyG and lifestyle trajectories and the stratification of ischemic stroke risk among non-diabetics. The TyG index is a valuable indicator for assessing insulin resistance. However, the potential benefits of lifestyle changes for those with significantly high TyG levels need to be clarified by more research to develop more effective stroke prevention strategies.
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Biomarcadores , Glicemia , Resistência à Insulina , AVC Isquêmico , Estilo de Vida , Comportamento de Redução do Risco , Triglicerídeos , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , AVC Isquêmico/sangue , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico , Fatores de Risco , Medição de Risco , Biomarcadores/sangue , Glicemia/metabolismo , China/epidemiologia , Idoso , Triglicerídeos/sangue , Fatores de Tempo , Adulto , Prognóstico , Estilo de Vida SaudávelRESUMO
Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(-) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05-1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00-1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06-1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00-1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis.
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Citocinas , Vírus da Hepatite B , Hepatite B , Transmissão Vertical de Doenças Infecciosas , Receptor Toll-Like 9 , Humanos , Feminino , Gravidez , Estudos Transversais , Hepatite B/transmissão , Hepatite B/sangue , Hepatite B/imunologia , China/epidemiologia , Adulto , Citocinas/sangue , Vírus da Hepatite B/imunologia , Recém-Nascido , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , DNA Viral/sangue , Interferon gama/sangue , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/virologiaRESUMO
PURPOSE: The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear. METHODS: This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves. RESULTS: Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors. CONCLUSION: The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B , Nucleotídeos , Interleucina-8 , Citocinas/metabolismo , Antivirais/uso terapêuticoRESUMO
Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity and angiotensin-converting enzyme (ACE)-inhibitory activity. Based on the optimization of the hydrolysis parameters of protease A69, a process for PPs preparation was set up in which the peanut protein was hydrolyzed by A69 at 3000 U g-1 and 60 °C, pH 7.0 for 4 h. The prepared PPs exhibited a high content of peptides with molecular weights lower than 1000 Da (>80%) and 3000 Da (>95%) and contained 17 kinds of amino acids. Moreover, the PPs displayed elevated scavenging of hydroxyl radical and 1,1-diphenyl-2-picryl-hydrazyl radical, with IC50 values of 1.50 mg mL-1 and 1.66 mg mL-1, respectively, indicating the good antioxidant activity of the PPs. The PPs also showed remarkable ACE-inhibitory activity, with an IC50 value of 0.71 mg mL-1. By liquid chromatography mass spectrometry analysis, the sequences of 19 ACE inhibitory peptides and 15 antioxidant peptides were identified from the PPs. These results indicate that the prepared PPs have a good nutritional value, as well as good antioxidant and antihypertensive effects, and that the marine bacterial metalloprotease A69 has promising potential in relation to the preparation of bioactive peptides from peanut protein.
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Inibidores da Enzima Conversora de Angiotensina , Antioxidantes , Arachis , Bacillus subtilis , Metaloproteases , Peptídeos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Antioxidantes/farmacologia , Antioxidantes/química , Metaloproteases/química , Metaloproteases/farmacologia , Arachis/química , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/enzimologia , Peptídeos/farmacologia , Peptídeos/química , Hidrólise , Peptidil Dipeptidase A/metabolismo , Peptidil Dipeptidase A/químicaRESUMO
The persistent double layer structure whereby two layers with different properties form at the front and rear of absorbers is a critical challenge in the field of kesterite thin-film solar cells, which imposes additional nonradiative recombination in the quasi-neutral region and potential limitation to the transport of hole carriers. Herein, an effective model for growing monolayer CZTSe thin-films based on metal precursors with large grains spanning the whole film is developed. Voids and fine grain layer are avoided successfully by suppressing the formation of a Sn-rich liquid metal phase near Mo back contact during alloying, while grain coarsening is greatly promoted by enhancing mass transfer during grain growth. The desired morphology exhibits several encouraging features, including significantly reduced recombination in the quasi-neutral region that contributes to the large increase of short-circuit current, and a quasi-Ohmic back contact which is a prerequisite for high fill factor. Though this growth mode may introduce more interfacial defects which require further modification, the strategies demonstrated remove a primary obstacle toward higher efficiency kesterite solar cells, and can be applicable to morphology control with other emerging chalcogenide thin films.
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Small grain size and near-horizontal grain boundaries are known to be detrimental to the carrier collection efficiency and device performance of pure-sulfide Cu2 ZnSnS4 (CZTS) solar cells. However, forming large grains spanning the absorber layer while maintaining high electronic quality is challenging particularly for pure sulfide CZTS. Herein, a liquid-phase-assisted grain growth (LGG) model that enables the formation of large grains spanning across the CZTS absorber without compromising the electronic quality is demonstrated. By introducing a Ge-alloyed CZTS nanoparticle layer at the bottom of the sputtered precursor, a Cu-rich and Sn-rich liquid phase forms at the high temperature sulfurization stage, which can effectively remove the detrimental near-horizontal grain boundaries and promote grain growth, thus greatly improving the carrier collection efficiency and reducing nonradiative recombination. The remaining liquid phase layer at the rear interface shows a high work function, acting as an effective hole transport layer. The modified morphology greatly increases the short-circuit current density and fill factor, enabling 10.3% efficient green Cd-free CZTS devices. This work unlocks a grain growth mechanism, advancing the morphology control of sulfide-based kesterite solar cells.
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OBJECTIVES: Preeclampsia with severe features (PECsf) is a common disease in pregnant women. let-7a and IFN-gamma (interferon-gamma) are involved in diagnosis and prognosis of preeclampsia. This study explored effects of let-7a and IFN-gamma on PECsf patients. METHODS: The placental tissue of 21 PECsf, 19 preeclampsia without severe features (PEC), and 20 normal pregnant women were collected, and clinical data were recorded. let-7a and IFN-gamma expressions in placental tissue were detected. The correlation between let-7a/IFN-gamma expression and clinical indexes was analyzed. According to let-7a and IFN-gamma expressions, PECsf patients were assigned into Hlet-7a group (let-7a high expression group), Llet-7a group (let-7a low expression group), HIFN-gamma group (IFN-gamma high expression group) and LIFN-gamma group (IFN-gamma low expression group). The incidence of adverse prognosis was compared. RESULTS: let-7a and IFN-gamma were highly expressed in placental tissue of preeclampsia patients, with significant differences between PEC and PECsf. The high expressions of let-7a and IFN-gamma were positively correlated with mean arterial pressure, lactate dehydrogenase, and 24 h urinary protein in placental tissues of PECsf patients. High let-7a and IFN-gamma expressions were correlated with adverse outcomes of PECsf. CONCLUSIONS: High let-7a and IFN-gamma expressions were correlated with clinical features, and could be used as biomarkers for treatment and poor prognosis of PECsf.
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MicroRNAs , Pré-Eclâmpsia , Biomarcadores , Feminino , Humanos , Interferon gama , Lactato Desidrogenases , MicroRNAs/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/diagnóstico , GravidezRESUMO
Methanol is assimilated through the serine cycle to generate acetyl-CoA without carbon loss. However, a highly active serine cycle requires high consumption of reducing equivalents and ATP, thereby leading to the impaired efficiency of methanol conversion to reduced chemicals. In the present study, a genome-scale flux balance analysis (FBA) predicted that the introduction of the heterologous ribulose monophosphate (RuMP) cycle, a more energy-efficient pathway for methanol assimilation, could theoretically increase growth rate by 31.3% for the model alphaproteobacterial methylotroph Methylorubrum extorquens AM1. Based on this analysis, we constructed a novel synergistic assimilation pathway in vivo by incorporating the RuMP cycle into M. extroquens metabolism with the intrinsic serine cycle. We demonstrated that the operation of the synergistic pathway could increase cell growth rate by 16.5% and methanol consumption rate by 13.1%. This strategy rewired the central methylotrophic metabolism through adjusting core gene transcription, leading to a pool size increase of C2 to C5 central intermediates by 1.2- to 3.6-fold and an NADPH cofactor improvement by 1.3-fold. The titer of 3-hydroxypropionic acid (3-HP), a model product in the newly engineered chassis of M. extorquens AM1, was increased to 91.2 mg/L in shake-flask culture, representing a 3.1-fold increase compared with the control strain with only the serine cycle. The final titer of 3-HP was significantly improved to 0.857 g/L in the fed-batch bioreactor, which was more competitive compared with the other 3-HP producers using methane and CO2 as C1 sources. Collectively, our current study demonstrated that engineering the synergistic methanol assimilation pathway was a promising strategy to increase the carbon assimilation and the yields of reduced chemicals in diverse host strains for C1 microbial cell factories.
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Metanol , Methylobacterium extorquens , Acetilcoenzima A , Methylobacterium extorquens/genética , PentosesRESUMO
Background: Hypertension (HTN), dyslipidemia and hyperhomocysteinemia (HHcy) are risk factors for cardiovascular disease (CVD).Methods: Hypertensive Chinese subjects (n = 228) were enrolled. MTHFR C667T, MTHFR A1298C, MTR A2756G, and MTRR A66G genotypes were determined. Unconditional logistic regression was performed to determine the associations of serum Hcy status and genotypes with HTN and dyslipidemia.Results: The mean age of hypertensive adults was 65.53 ± 9.94 years, including 88 (38.6%) men and 140 (61.4%) women. Patients with MTHFR 667TT and MTRR GG carriers showed higher serum Hcy levels (P = 0.019 and 0.018, respectively), which is associated with higher serum triacylglycerols (TAG) and total cholesterol (TC) levels (P = 0.014 and 0.044, respectively) and a higher risk for hypertriglyceridemia (OR = 1.889, 95% CI: 1.105-3.229, P = 0.020). Compared with low Hcy and MTRR 66AA, those with high Hcy and 66AA or 66AG+GG showed higher odd\s of hypertriglyceridemia (MTRR 66AA+ high Hcy: OR: 2.692, 95% CI: 1.189-6.096, Pcombined = 0.018; MTRR 66AG/GG+ high Hcy: OR: 3.433, 95% CI: 1.517-7.772, Pcombined = 0.003, respectively). Patients with high Hcy and MTHFR 667CC, as well as those with low Hcy and 667CT+TT, showed lower odds of uncontrolled SBP (MTHFR 667CC+ high Hcy: OR: 0.338, 95% CI: 0.115-0.996, Pcombined = 0.049; MTHFR 667CT/TT+ low Hcy: OR: 0.421, 95% CI: 0.193-0.921, Pcombined = 0.030) compared to patients with low Hcy and MTHFR 667CC.Conclusions: Serum Hcy status and Hcy metabolism gene polymorphisms (MTHFR C667T and MTRR A66G) may have synergistic effects on the prevalence of HTN and dyslipidemia.
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Ferredoxina-NADP Redutase/genética , Homocisteína/sangue , Hipertensão/genética , Hipertrigliceridemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Idoso , Povo Asiático/genética , Colesterol/sangue , Feminino , Ácido Fólico , Heterozigoto , Humanos , Hipertensão/sangue , Hipertrigliceridemia/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Triglicerídeos/sangueRESUMO
Methanol, commercially generated from methane, is a renewable chemical feedstock that is highly soluble, relatively inexpensive, and easy to handle. The concept of native methylotrophic bacteria serving as whole cell catalysts for production of chemicals and materials using methanol as a feedstock is highly attractive. In recent years, the available omics data for methylotrophic bacteria, especially for Methylobacterium extorquens, the most well-characterized model methylotroph, have provided a solid platform for rational engineering of methylotrophic bacteria for industrial production. In addition, there is a strong interest in converting the more traditional heterotrophic production platforms toward the use of single carbon substrates, including methanol, through metabolic engineering. In this chapter, we review the recent progress toward achieving the desired growth and production yields from methanol, by genetically engineered native methylotrophic strains and by the engineered synthetic methylotrophs.
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Produtos Biológicos/metabolismo , Biotransformação/fisiologia , Engenharia Metabólica/métodos , Metanol/metabolismo , Methylobacterium extorquens , Organismos Geneticamente Modificados , Redes e Vias Metabólicas/genética , Metano/metabolismo , Methylobacterium extorquens/genética , Methylobacterium extorquens/metabolismo , Biologia Sintética/métodosRESUMO
Candida albicans and Cryptococcus neoformans, human-pathogenic fungi found worldwide, are receiving increasing attention due to high morbidity and mortality in immunocompromised patients. In the present work, 110 fungus pairs were constructed by coculturing 16 wood-decaying basidiomycetes, among which coculture of Trametes robiniophila Murr and Pleurotus ostreatus was found to strongly inhibit pathogenic fungi through bioactivity-guided assays. A combination of metabolomics and molecular network analysis revealed that 44 features were either newly synthesized or produced at high levels in this coculture system and that 6 of the features that belonged to a family of novel and unusual linear sesterterpenes contributed to high activity with MICs of 1 to 32 µg/ml against pathogenic fungi. Furthermore, dynamic 13C-labeling analysis revealed an association between induced features and the corresponding fungi. Unusual sesterterpenes were 13C labeled only in P. ostreatus in a time course after stimulation by the coculture, suggesting that these sesterterpenes were synthesized by P. ostreatus instead of T. robiniophila Murr. Sesterterpene compounds 1 to 3 were renamed postrediene A to C. Real-time reverse transcription-quantitative PCR (RT-qPCR) analysis revealed that transcriptional levels of three genes encoding terpene synthase, farnesyl-diphosphate farnesyltransferase, and oxidase were found to be 8.2-fold, 88.7-fold, and 21.6-fold higher, respectively, in the coculture than in the monoculture, indicating that biosynthetic gene cluster 10 was most likely responsible for the synthesis of these sesterterpenes. A putative biosynthetic pathway of postrediene A to postrediene C was then proposed based on structures of sesterterpenes and molecular network analysis.IMPORTANCE A number of gene clusters involved in biosynthesis of secondary metabolites are presumably silent or expressed at low levels under conditions of standard laboratory cultivation, resulting in a large gap between the pool of discovered metabolites and genome capability. This work mimicked naturally occurring competition by construction of an artificial coculture of basidiomycete fungi for the identification of secondary metabolites with novel scaffolds and excellent bioactivity. Unusual linear sesterterpenes of postrediene A to C synthesized by P. ostreatus not only were promising lead drugs against human-pathogenic fungi but also highlighted a distinct pathway for sesterterpene biosynthesis in basidiomycetes. The current work provides an important basis for uncovering novel gene functions involved in sesterterpene synthesis and for gaining insights into the mechanism of silent gene activation in fungal defense.
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Antifúngicos/farmacologia , Pleurotus/metabolismo , Sesterterpenos/metabolismo , Trametes/metabolismo , Candida albicans/efeitos dos fármacos , Técnicas de Cocultura , Cryptococcus neoformans/efeitos dos fármacos , Sesterterpenos/farmacologiaRESUMO
Evidence for blood pressure-lowering effects of vitamin C (VC) supplementation in clinical trials is inconsistent and limited studies have examined the effect of VC supplementation on hypertension (HTN) control. In this study, eligible patients were cluster assigned to receive 300 mg VC per day or nothing for 6 months. During the 6-month follow-up period, a questionnaire survey was obtained and standardized blood pressure measurements were performed on all subjects. Oral administration of VC significantly decreased the diastolic blood pressure and pulse pressure with a significant increase in HTN control. After adjusting for confounding variables, treatment with VC was associated with ~ 0.5 risk reduction of uncontrolled HTN in subjects received anti-hypertensive medications, whereas lower indoor and outdoor and ground temperature were significantly associated with an increased risk of uncontrolled HTN in all patients. Our results warrant further studies investigating the mechanisms underlying the association between VC and HTN control.
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Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Essencial/tratamento farmacológico , Hipertensão Essencial/fisiopatologia , Temperatura , Idoso , Anti-Hipertensivos/uso terapêutico , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Butadiene is a platform chemical used as an industrial feedstock for the manufacture of automobile tires, synthetic resins, latex and engineering plastics. Currently, butadiene is predominantly synthesized as a byproduct of ethylene production from non-renewable petroleum resources. Although the idea of biological synthesis of butadiene from sugars has been discussed in the literature, success for that goal has so far not been reported. As a model system for methanol assimilation, Methylobacterium extorquens AM1 can produce several unique metabolic intermediates for the production of value-added chemicals, including crotonyl-CoA as a potential precursor for butadiene synthesis. RESULTS: In this work, we focused on constructing a metabolic pathway to convert crotonyl-CoA into crotyl diphosphate, a direct precursor of butadiene. The engineered pathway consists of three identified enzymes, a hydroxyethylthiazole kinase (THK) from Escherichia coli, an isopentenyl phosphate kinase (IPK) from Methanothermobacter thermautotrophicus and an aldehyde/alcohol dehydrogenase (ADHE2) from Clostridium acetobutylicum. The Km and kcat of THK, IPK and ADHE2 were determined as 8.35 mM and 1.24 s-1, 1.28 mM and 153.14 s-1, and 2.34 mM and 1.15 s-1 towards crotonol, crotyl monophosphate and crotonyl-CoA, respectively. Then, the activity of one of rate-limiting enzymes, THK, was optimized by random mutagenesis coupled with a developed high-throughput screening colorimetric assay. The resulting variant (THKM82V) isolated from over 3000 colonies showed 8.6-fold higher activity than wild-type, which helped increase the titer of crotyl diphosphate to 0.76 mM, corresponding to a 7.6% conversion from crotonol in the one-pot in vitro reaction. Overexpression of native ADHE2, IPK with THKM82V under a strong promoter mxaF in M. extorquens AM1 did not produce crotyl diphosphate from crotonyl-CoA, but the engineered strain did generate 0.60 µg/mL of intracellular crotyl diphosphate from exogenously supplied crotonol at mid-exponential phase. CONCLUSIONS: These results represent the first step in producing a butadiene precursor in recombinant M. extorquens AM1. It not only demonstrates the feasibility of converting crotonol to key intermediates for butadiene biosynthesis, it also suggests future directions for improving catalytic efficiency of aldehyde/alcohol dehydrogenase to produce butadiene precursor from methanol.
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Butadienos/síntese química , Ensaios de Triagem em Larga Escala/métodos , Engenharia Metabólica/métodos , Methylobacterium extorquens/patogenicidade , Redes e Vias MetabólicasRESUMO
Transcatheter aortic valve implantation (TAVI) was originally devised as a treatment for patients with aortic stenosis (AS). It has since emerged as a beneficial alternative to surgical aortic valve replacement (SAVR), extending its reach to a broader array of patients. Our objective was to illustrate the developmental trends and focus areas in TAVI research. We sourced a total of 11,480 research papers on TAVI, published between 1994 and 2022, from the Web of Science Core Collection (WoSCC) database. We conducted a bibliometric analysis of these publications, generating cooperation maps, performing co-citation analysis of journals and references, and carrying out a cluster analysis of keywords. Our findings indicate that TAVI research grapples with numerous clinical challenges. We created knowledge maps that highlight contributing countries/institutions, authors, journals with high publication and citation rates, and notable references in this domain. North America and Europe have been at the forefront of research within the TAVI field. The institutions and authors from these regions exert significant influence in this area of study. Beginning in 2009, China has progressively expanded its research on TAVI over the past two decades. We anticipate that future research will increasingly focus on three key areas: implementation scope, lifelong management, outcomes and predicting the risk of TAVI. Research on TAVI is flourishing. Cooperation among different countries and institutions in this field must be strengthened in the future, especially for developing counties.
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Antifungal peptides are an appealing alternative to standard antifungal medicines due to their unique mechanism of action and low-level resistance. However, their susceptibility to protease degradation keeps hindering their future development. Herein, a library was established to design peptides with protease resistance and high antifungal activity. The peptides were incorporated with minimal D-amino acids to further improve the protease stability. The most active peptide, IR3, demonstrated good antifungal activity and low toxicity, and its molecular integrity was maintained after protease hydrolysis for 8 h at 2 mg/mL. Furthermore, IR3 could permeate the fungal cell wall, disrupt the cell membrane, produce reactive oxygen species, and induce apoptosis in fungal cells. In vivo experiments confirmed that IR3 could effectively treat fungal keratitis. Collectively, these findings suggest that IR3 is a promising antifungal agent and may be beneficial in the design and development of protease-resistant antifungal peptides.
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Aminoácidos , Antifúngicos , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Aminoácidos/química , Aminoácidos/farmacologia , Aminoácidos/metabolismo , Desenho de Fármacos , Animais , Proteólise/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/metabolismo , Candida albicans/efeitos dos fármacos , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Peptídeo Hidrolases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Aim: This study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship. Methods: This cross-sectional study enrolled participants aged >20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences. Results: A total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (P non-linear < 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, <50 IU/L) and then plateaued when ALT and GGT levels were >50 IU/L. Elevated AST within a certain range (range, <35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (>35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence. Conclusion: Liver enzymes were non-linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.
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Diabetes Mellitus Tipo 2 , Humanos , Adulto Jovem , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Inquéritos Nutricionais , Estudos Transversais , Alanina Transaminase , FígadoRESUMO
Aim: Multiple studies have investigated the association between alanine aminotransferase (ALT) and diabetes mellitus (DM); however, only a few studies have specifically examined the relationship between ALT and diabetic kidney disease (DKD). This study aimed to investigate the relationship between ALT and DKD using clinical data. Methods: A cross-sectional study was conducted on 668 individuals that included non-DM (N=281), DM without DKD (N=160), and DKD (N=227) patients. A generalized additive model (GAM) was used to examine the dose-response relationship between ALT and DKD risk. We also analyzed the data from the US National Health and Nutrition Examination Survey (NHANES) 2015-2018 using the same statistical methods; 4481, 1110, and 671 individuals were included in the non-DM, DM without DKD, and DKD groups, respectively. Results: The changes in ALT activity among the non-DM, DM without DKD, and DKD groups showed a similar pattern in both our clinical data and the NHANES dataset. ALT activity increases with the onset of DM, whereas ALT activity decreases when DM progresses to DKD. The GAM revealed a nonlinear U-shaped relationship between ALT and DKD risk in the two datasets, and the lowest range of ALT was 40-50 IU/L. Both lower (<40 IU/L) and higher (>50 IU/L) ALT activity were found to be positively associated with DKD risk. Conclusion: A U-shaped nonlinear association between ALT and DKD was found in our clinical data and NHANES data. DKD risk was increased by both lower or higher ALT activity. To confirm the causality of nonlinear relationship, larger prospective studies or Mendelian randomization analysis are required.
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Coastal heavy-metal contamination poses significant risks to marine ecosystems and human health, necessitating comprehensive research for effective mitigation strategies. This study assessed heavy-metal pollution in sediments, seawater, and organisms in the Pearl River Estuary (PRE), with a focus on Cd, Cu, Pb, Zn, As, Hg, and Cr. A notable reduction in heavy metal concentrations in surface sediments was observed in 2020 compared to 2017 and 2018, likely due to improved pollution management and COVID-19 pandemic restrictions. Spatial analysis revealed a positive correlation between elevated heavy-metal concentrations (Cu, Pb, Zn, Cd, and As) and areas with significant human activity. Source analysis indicated that anthropogenic activities accounted for 63 % of the heavy metals in sediments, originating from industrial effluents, metal processing, vehicular activities, and fossil fuel combustion. Cd presented a high ecological risk due to its significant enrichment in surface sediments. Organisms in the PRE were found to be relatively enriched with Hg and Cu, with average As concentrations slightly exceeding the Chinese food-health criterion. This study identified high-risk ecological zones and highlighted Cd as the primary pollutant in the PRE. The findings demonstrate the effectiveness of recent pollution control measures and emphasize the need for ongoing monitoring and mitigation to safeguard marine ecosystems and human health.
RESUMO
The Cd-free Cu2 ZnSnS4 (CZTS) solar cell is an ideal candidate for producing low-cost clean energy through green materials owing to its inherent environmental friendliness and earth abundance. Nevertheless, sulfide CZTS has long suffered from severe open-circuit voltage (VOC ) deficits, limiting the full exploitation of performance potential and further progress. Here, an effective strategy is proposed to alleviate the nonradiative VOC loss by manipulating the phase evolution during the critical kesterite phase formation stage. With a Ge cap layer on the precursor, premature CZTS grain formation is suppressed at low temperatures, leading to fewer nucleation centers at the initial crystallization stage. Consequently, the CZTS grain formation and crystallization are deferred to high temperatures, resulting in enhanced grain interior quality and less unfavorable grain boundaries in the final film. As a result, a champion efficiency of 10.7% for Cd-free CZTS solar cells with remarkably high VOC beyond 800 mV (63.2% Schockley-Queisser limit) is realized, indicating that nonradiative recombination is effectively inhibited. This strategy may advance other compound semiconductors seeking high-quality crystallization.