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While engineered DNA nanoframeworks have been extensively exploited for delivery of diagnostic and therapeutic regents, DNA tiling-based DNA frameworks amenable to applications in living systems lag much behind. In this contribution, by developing a Y-shaped backbone-based DNA tiling technique, we assemble Y-shaped backbone-rigidified supersized DNA tetrahedrons (RDT) with 100% efficiency for precisely targeted tumor therapy. RDT displays unparalleled rigidness and unmatched resistance to nuclease degradation so that it almost does not deform under the force exerted by the atomic force microscopy tip, and the residual amount is not less than 90% upon incubating in biological media for 24 h, displaying at least 11.6 times enhanced degradation resistance. Without any targeting ligand, RDT enters the cancer cell in a targeted manner, and internalization specificity is up to 15.8. Moreover, 77% of RDT objects remain intact within living cells for 14 h. The drug loading content of RDT is improved by 4-8 times, and RDT almost 100% eliminates the unintended drug leakage in a stimulated physiological medium. Once systemically administrated into HeLa tumor-bearing mouse models, doxorubicin-loaded RDTs preferentially accumulate in tumor sites and efficiently suppress tumor growth without detectable off-target toxicity. The Y-DNA tiling technique offers invaluable insights into the development of structural DNA nanotechnology for precise medicine.
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DNA , Neoplasias , Humanos , Animais , Camundongos , Microscopia de Força Atômica , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Células HeLa , Neoplasias/tratamento farmacológicoRESUMO
In this Letter, a surface wave, the Pearcey Talbot-like plasmon, which has the properties of self-imaging and multiple autofocusing, is presented as a novel, to the best of our knowledge, plasmonic bottle array generation scheme. With originality, the overall structure and the partial intensity of the plasmonic bottle array can be adjusted through the initial input, and modifying the Pearcey function enables the plasmonic bottle array to exhibit self-bending characteristics, which makes particle capture and manipulation easier and more flexible. A scheme to generate the plasmon is proposed, and we prove it by the finite-difference time-domain numerical simulations.
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Pollution control and carbon emission reduction pose significant challenges for developing countries, and achieving synergistic reductions in pollution and carbon emissions (SRPCs) has emerged as the optimal choice. Digitization, a prevailing trend in the current era, presents new opportunities for realizing the SRPC. We utilize data from Chinese A-share listed companies from 2007 to 2022 to investigate the impact of corporate digital transformation on the SRPC. The research reveals the following. (1) Enterprise digital transformation significantly promotes the SRPC, a conclusion validated through a series of robustness tests. However, the SRPC resulting from digital transformation is characterized by weak synergy, which is primarily observed in the coordinated reduction in air pollution and carbon emissions. (2) This effect is notably stronger for companies near environmental regulatory authorities, those receiving government environmental subsidies, and state-owned enterprises (SOEs). (3) Enhancing managerial collaborative management capabilities, promoting corporate technological innovation capabilities, and alleviating financing pressure are the primary mechanisms at play. This research provides important policy and practical insights for promoting the SRPC in the context of digitization, fostering sustainable development.
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PURPOSE: Determine the prevalence and influencing factors of patient delay in stroke patients and explore variation in prevalence by country and delayed time. METHODS: PubMed, The Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), Weipu database, and Wanfang database were comprehensively searched for observational studies from inception to April, 2023. The pooled prevalence, odds ratio (OR), and 95% confidence intervals (CI) were calculated with Stata 16.0 software. RESULTS: In total, 2721 articles were screened and data from 70 studies involving 85,468 subjects were used in meta-analysis. The pooled prevalence of patient delay in stroke patients was 59% (95% CI, 0.54-0.64). The estimates of pooled prevalence calculated for African, Asian, and European patient delay in stroke patients were 55% (0.29-0.81), 61% (0.56-0.66), and 49% (0.34-0.64).According to the patient delay time, the prevalence of 6 h, 5 h, 4.5 h, 3.5 h, 3 h and 2 h were 54% (0.47-0.61), 73% (0.61-0.86), 60% (0.49-0.71), 81% (0.68-0.93), 52% (0.42-0.62), 63% (0.19-1.07). Distance from the place of onset to the hospital > 10 km [OR=2.49, 95%CI (1.92, 3.24)], having medical insurance [OR = 0.45, 95%CI (0.26,0.80)], lack of stroke-related knowledge [OR = 1.56, 95%CI (1.08,2.26)], education level below junior high school [OR = 1.69, 95%CI (1.22,2.36)], non-emergency medical services (Non-EMS) [OR = 2.10, 95%CI (1.49,2.97)], living in rural areas [OR = 1.54, 95%CI (1.15,2.07)], disturbance of consciousness [OR = 0.60, 95%CI (0.39,0.93)], history of atrial fibrillation [OR = 0.53, 95%CI (0.47,0.59)], age ≥ 65 years [OR = 1.18, 95%CI (1.02,1.37)], National institutes of health stroke scale (NIHSS) ≤ 4 points [OR= 2.26, 95%CI (1.06,4.79)]were factors for patient delay in stroke patients. CONCLUSIONS: The prevalence of patient delay in stroke patients is high, we should pay attention to the influencing factors of patient delay in stroke patients and provide a theoretical basis for shortening the treatment time of stroke patients.
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Acidente Vascular Cerebral , Tempo para o Tratamento , Humanos , Acidente Vascular Cerebral/epidemiologia , Prevalência , Fatores de TempoRESUMO
BACKGROUND: Predicting the long-term survival in adenoid cystic carcinoma (ACC) patients remains challenging. Inflammatory cell-based indices are emerging as prognostic indicators of oncology. PURPOSE: This study aimed to determine the associations between the preoperative systemic inflammatory response index (SIRI) and the systemic immunoinflammatory index (SII) and the 10-year survival rates in patients with ACC of the head and neck (ACCHN). STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study comprised ACCHN patients treated at the Chinese People's Liberation Army General Hospital between November 2003 and December 2020. PREDICTOR VARIABLE: The inflammatory response, assessed using the SIRI and SII, was the predictor variable. The optimal cutoff values were based on the maximum Youden index values (sensitivity ï¼ specificityï¼1). The patients were divided into two groups each, based on the SIRI (low, ≤ 0.15) and (high, > 0.15), and SII (low, ≤ 562.8 and high, > 562.8) values. MAIN OUTCOME VARIABLE(S): Overall survival (OS), or the number of days, weeks, or months between treatment initiation and death (or the last follow-up date), was the primary outcome variable. COVARIATES: The covariates were classified as demographic (age, gender, body mass index), medical (hypertension, diabetes), inflammatory (neutrophils, lymphocytes, monocytes, platelets, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, neutrophil-lymphocyte ratio), and perioperative (tumor stage, lymph node metastasis, tumor size, treatment type). ANALYSES: Descriptive, univariate, and multivariate Cox proportional risk regression analyses were performed to determine whether the SIRI and SII were independent prognostic factors for OS. Kaplan-Meier survival curves and log-rank tests were used to determine their associations with the OS. RESULTS: The study sample comprised 162 patients (mean age, 52 ± 14; males, 39.5%). The median follow-up time was 6.81 ± 0.23, and the 10-year OS rate was 7.68 ± 0.25. The low and high SIRI groups comprised 109 and 53 patients, while the low and high SII groups comprised 116 and 46 patients, respectively. SIRI was identified as a prognostic factor (P < .01; hazard ratio, 2.45; 95% confidence interval, 1.35-4.45). CONCLUSION AND RELEVANCE: The SIRI has the advantages of reproducibility, convenience, noninvasiveness, and affordability, making it a promising prognostic inflammatory index for patients with ACCHN.
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Carcinoma Adenoide Cístico , Humanos , Masculino , Feminino , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Taxa de Sobrevida , Adulto , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/imunologia , Prognóstico , IdosoRESUMO
Wickerhamomyces anomalus is one of the most important ester-producing strains in Chinese baijiu brewing. Ethanol and lactic acid are the main metabolites produced during baijiu brewing, but their synergistic influence on the growth and ester production of W. anomalus is unclear. Therefore, in this paper, based on the contents of ethanol and lactic acid during Te-flavor baijiu brewing, the effects of different ethanol concentrations (3, 6, and 9% (v/v)) combined with 1% lactic acid on the growth and ester production of W. anomalus NCUF307.1 were studied and their influence mechanisms were analyzed by transcriptomics. The results showed that the growth of W. anomalus NCUF307.1 under the induction of lactic acid was inhibited by ethanol. Although self-repair mechanism of W. anomalus NCUF307.1 induced by lactic acid was initiated at all concentrations of ethanol, resulting in significant up-regulation of genes related to the Genetic Information Processing pathway, such as cell cycle-yeast, meiosis-yeast, DNA replication and other pathways. However, the accumulation of reactive oxygen species and the inhibition of pathways associated with carbohydrate and amino acid metabolism may be the main reason for the inhibition of growth in W. anomalus NCUF307.1. In addition, 3% and 6% ethanol combined with 1% lactic acid could promote the ester production of W. anomalus NCUF307.1, which may be related to the up-regulation of EAT1, ADH5 and TGL5 genes, while the inhibition in 9% ethanol may be related to down-regulation of ATF2, EAT1, ADH2, ADH5, and TGL3 genes.
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Ésteres , Etanol , Fermentação , Ácido Láctico , Saccharomycetales , Etanol/metabolismo , Ácido Láctico/metabolismo , Saccharomycetales/genética , Saccharomycetales/metabolismo , Saccharomycetales/efeitos dos fármacos , Saccharomycetales/crescimento & desenvolvimento , Ésteres/metabolismo , Transcriptoma , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão GênicaRESUMO
Load-bearing biological tissues, such as cartilage and muscles, exhibit several crucial properties, including high elasticity, strength, and recoverability. These characteristics enable these tissues to endure significant mechanical stresses and swiftly recover after deformation, contributing to their exceptional durability and functionality. In contrast, while hydrogels are highly biocompatible and hold promise as synthetic biomaterials, their inherent network structure often limits their ability to simultaneously possess a diverse range of superior mechanical properties. As a result, the applications of hydrogels are significantly constrained. This article delves into the design mechanisms and mechanical properties of various tough hydrogels and investigates their applications in tissue engineering, flexible electronics, and other fields. The objective is to provide insights into the fabrication and application of hydrogels with combined high strength, stretchability, toughness, and fast recovery as well as their future development directions and challenges.
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Materiais Biocompatíveis , Hidrogéis , Hidrogéis/química , Materiais Biocompatíveis/química , Engenharia Tecidual , Elasticidade , CartilagemRESUMO
BACKGROUND AND PURPOSE: Post-stroke cognitive impairment (PSCI) is a frequent consequence of stroke, which affects the quality of life and prognosis of stroke survivors. Numerous studies have indicated that blood biomarkers may be the key determinants for predicting and diagnosing cognitive impairment, but the results remain varied. Therefore, this meta-analysis aims to summarize potential biomarkers associated with PSCI. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched for studies exploring blood biomarkers associated with PSCI from inception to 15 April 2022. RESULTS: 63 studies were selected from 4,047 references, which involves 95 blood biomarkers associated with the PSCI. We meta-analyzed 20 potential blood biomarker candidates, the results shown that the homocysteine (Hcy) (SMD = 0.35; 95 %CI: 0.20-0.49; P < 0.00001), c-reactive protein (CRP) (SMD = 0.49; 95 %CI: 0.20-0.78; P = 0.0008), uric acid (UA) (SMD = 0.41; 95 %CI: 0.06-0.76; P = 0.02), interleukin 6 (IL-6) (SMD = 0.92; 95 % CI: 0.27-1.57; P = 0.005), cystatin C (Cys-C) (SMD = 0.58; 95 %CI: 0.28-0.87; P = 0.0001), creatinine (SMD = 0.39; 95 %CI: 0.23-0.55; P < 0.00001) and tumor necrosis factor alpha (TNF-α) (SMD = 0.45; 95 %CI: 0.08-0.82; P = 0.02) levels were significantly higher in patients with PSCI than in the non-PSCI group. CONCLUSION: Based on our findings, we recommend that paramedics focus on the blood biomarkers levels of Hcy, CRP, UA, IL-6, Cys-C, creatinine and TNF-α in conjunction with neuroimaging and neuropsychological assessment to assess the risk of PSCI, which may help with early detection and timely preventive measures. At the same time, other potential blood biomarkers should be further validated in future studies.
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Biomarcadores , Cognição , Disfunção Cognitiva , Valor Preditivo dos Testes , Acidente Vascular Cerebral , Humanos , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/complicações , Idoso , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Japanese encephalitis virus (JEV) remains a predominant cause of Japanese encephalitis (JE) globally. Its infection is usually accompanied by disrupted bloodâbrain barrier (BBB) integrity and central nervous system (CNS) inflammation in a poorly understood pathogenesis. Productive JEV infection in brain microvascular endothelial cells (BMECs) is considered the initial event of the virus in penetrating the BBB. Type I/III IFN and related factors have been described as negative regulators in CNS inflammation, whereas their role in JE remains ambiguous. METHODS: RNA-sequencing profiling (RNA-seq), real-time quantitative PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze the gene and protein expression changes between mock- and JEV-infected hBMECs. Bioinformatic tools were used to cluster altered signaling pathway members during JEV infection. The shRNA-mediated immune factor-knockdown hBMECs and the in vitro transwell BBB model were utilized to explore the interrelation between immune factors, as well as between immune factors and BBB endothelial integrity. RESULTS: RNA-Seq data of JEV-infected hBMECs identified 417, 1256, and 2748 differentially expressed genes (DEGs) at 12, 36, and 72 h post-infection (hpi), respectively. The altered genes clustered into distinct pathways in gene ontology (GO) terms and KEGG pathway enrichment analysis, including host antiviral immune defense and endothelial cell leakage. Further investigation revealed that pattern-recognition receptors (PRRs, including TLR3, RIG-I, and MDA5) sensed JEV and initiated IRF/IFN signaling. IFNs triggered the expression of interferon-induced proteins with tetratricopeptide repeats (IFITs) via the JAK/STAT pathway. Distinct PRRs exert different functions in barrier homeostasis, while treatment with IFN (IFN-ß and IFN-λ1) in hBMECs stabilizes the endothelial barrier by alleviating exogenous destruction. Despite the complex interrelationship, IFITs are considered nonessential in the IFN-mediated maintenance of hBMEC barrier integrity. CONCLUSIONS: This research provided the first comprehensive description of the molecular mechanisms of hostâpathogen interplay in hBMECs responding to JEV invasion, in which type I/III IFN and related factors strongly correlated with regulating the hBMEC barrier and restricting JEV infection. This might help with developing an attractive therapeutic strategy in JE.
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Vírus da Encefalite Japonesa (Espécie) , Vírus da Encefalite Japonesa (Subgrupo) , Encefalite Japonesa , Interferon Tipo I , Humanos , Encefalite Japonesa/genética , Barreira Hematoencefálica , Interferon lambda , Células Endoteliais , Janus Quinases , Fatores de Transcrição STAT , Transdução de Sinais , InflamaçãoRESUMO
In this Letter, we introduce a new, to the best of our knowledge, class of accelerating surface plasmonic wave: the Olver plasmon. Our research reveals that such a surface wave propagates along self-bending trajectories at the silver-air interface with various orders, among which Airy plasmon is regarded as the zeroth-order one. We demonstrate a plasmonic autofocusing hot-spot by the interference of Olver plasmons and the focusing properties can be controlled. Also, a scheme for the generation of this new surface plasmon is proposed with the verification of finite difference time-domain numerical simulations.
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PGRP is a family of pattern recognition molecules of the innate immune system. PGRPs are conserved from insects to mammals and have diverse functions in antimicrobial defense. Here we cloned a common carp PGRP ortholog, CcPGRP2 containing a conserved C-terminal PGRP domain. We tested the expression levels of CcPGRP2 in the liver, spleen, kidney, foregut, midgut, and hindgut of the highest level in the liver. The expression of CcPGRP2 upregulated in common carp infected with Aeromonas hydrophila (A. hydrophila) or Staphylococcus aureus (S. aureus). Recombinant CcPGRP2 protein expressed in Escherichia coli (E. coli) system and the purified CcPGRP2 could maintain the integrity of intestinal mucosa of common carp infected with A. hydrophila. In addition, CcPGRP2 could agglutinate or bind both gram-positive and gram-negative bacteria in a Zn2+-dependent manner. CcPGRP2 has a stronger agglutination and bacterial binding ability in gram-positive bacteria than in gram-negative bacteria. It is perhaps because CcPGRP2 could bind peptidoglycan (PGN) with a higher degree to lipopolysaccharide (LPS). And CcPGRP2 shows antimicrobial activities in the presence of Zn2+. Our results of CcPGRP2 provided new insight into the function of PGRP in the innate immunity of the common carp.
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Infecções Bacterianas , Carpas , Animais , Escherichia coli , Staphylococcus aureus/metabolismo , Antibacterianos/metabolismo , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Imunidade Inata/genética , Carpas/genética , Carpas/metabolismo , Peptidoglicano/metabolismo , Mamíferos/metabolismoRESUMO
Uniformly narrowed internal carotid artery (ICA) without proximal steno-occlusion or parietal anomalies is often subject to misdiagnosis due to lack of awareness. We combined our experiences of 4 cases with 29 previously published cases to form a retrospective series including 18 cases of ICA hypoplasia and 15 cases of ICA acquired narrowing. The ultrasonic manifestations of ICA acquired narrowing and ICA hypoplasia are extremely similar, but narrowed ICA without intracranial occlusion or bottle-neck-sign highly indicates ICA hypoplasia, whereas moyamoya vessels favor ICA acquired narrowing, thus promoting the understanding of and discriminability between the two on neurovascular ultrasound.
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Estenose das Carótidas , Doença de Moyamoya , Humanos , Artéria Carótida Interna/diagnóstico por imagem , Estudos Retrospectivos , UltrassonografiaRESUMO
Inner-outer asymmetry, where the outer flanker induces stronger crowding than the inner flanker, is a hallmark property of visual crowding. It is unclear the contribution of inner-outer asymmetry to the pattern of crowding errors (biased predominantly toward the flanker identities) and the role of training on crowding errors. In a typical radial crowding display, 20 observers were asked to report the orientation of a target Gabor (7.5° eccentricity) flanked by either an inner or outer Gabor along the horizontal meridian. The results showed that outer flanker conditions induced stronger crowding, accompanied by assimilative errors to the outer flanker for similar target/flanker elements. In contrast, the inner flanker condition exhibited weaker crowding, with no significant patterns of crowding errors. A population coding model showed that the flanker weights in the outer flanker condition were significantly higher than those in the inner flanker condition. Nine observers continued to train the outer flanker condition for four sessions. Training reduced inner-outer asymmetry and reduced flanker weights to the outer flanker. The learning effects were retained over 4 to 6 months. Individual differences in the appearance of crowding errors, the strength of inner-outer asymmetry, and the training effects were evident. Nevertheless, our findings indicate that different crowding mechanisms may be responsible for the asymmetric crowding effects induced by inner and outer flankers, with the outer flankers dominating the appearance more than the inner ones. Training reduces inner-outer asymmetry by reducing target/flanker confusion, and learning is persistent over months, suggesting that perceptual learning has the potential to improve visual performance by promoting neural plasticity.
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Aglomeração , Campos Visuais , Humanos , Aprendizagem , Individualidade , Plasticidade Neuronal , Reconhecimento Visual de ModelosRESUMO
With the gradual integration of internet technology and the industrial control field, industrial control systems (ICSs) have begun to access public networks on a large scale. Attackers use these public network interfaces to launch frequent invasions of industrial control systems, thus resulting in equipment failure and downtime, production data leakage, and other serious harm. To ensure security, ICSs urgently need a mature intrusion detection mechanism. Most of the existing research on intrusion detection in ICSs focuses on improving the accuracy of intrusion detection, thereby ignoring the problem of limited equipment resources in industrial control environments, which makes it difficult to apply excellent intrusion detection algorithms in practice. In this study, we first use the spectral residual (SR) algorithm to process the data; we then propose the improved lightweight variational autoencoder (LVA) with autoregression to reconstruct the data, and we finally perform anomaly determination based on the permutation entropy (PE) algorithm. We construct a lightweight unsupervised intrusion detection model named LVA-SP. The model as a whole adopts a lightweight design with a simpler network structure and fewer parameters, which achieves a balance between the detection accuracy and the system resource overhead. Experimental results on the ICSs dataset show that our proposed LVA-SP model achieved an F1-score of 84.81% and has advantages in terms of time and memory overhead.
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The access control (AC) system in an IoT (Internet of Things) context ensures that only authorized entities have access to specific devices and that the authorization procedure is based on pre-established rules. Recently, blockchain-based AC systems have gained attention within research as a potential solution to the single point of failure issue that centralized architectures may bring. Moreover, zero-knowledge proof (ZKP) technology is included in blockchain-based AC systems to address the issue of sensitive data leaking. However, current solutions have two problems: (1) systems built by these works are not adaptive to high-traffic IoT environments because of low transactions per second (TPS) and high latency; (2) these works cannot fully guarantee that all user behaviors are honest. In this work, we propose a blockchain-based AC system with zero-knowledge rollups to address the aforementioned issues. Our proposed system implements zero-knowledge rollups (ZK-rollups) of access control, where different AC authorization requests can be grouped into the same batch to generate a uniform ZKP, which is designed specifically to guarantee that participants can be trusted. In low-traffic environments, sufficient experiments show that the proposed system has the least AC authorization time cost compared to existing works. In high-traffic environments, we further prove that based on the ZK-rollups optimization, the proposed system can reduce the authorization time overhead by 86%. Furthermore, the security analysis is presented to show the system's ability to prevent malicious behaviors.
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BACKGROUND: Bio-augmented Daqu is used to improve the microbial community and physicochemical parameters of fermented grains, thus affecting the flavor and quality of baijiu. This study investigated the effects of bio-augmented Daqu inoculated with Aspergillus niger NCUF413.1 and Saccharomyces cerevisiae NCUF304.1 on the microbial community, aroma compounds, and physicochemical parameters of fermented grains during special-flavor baijiu brewing. RESULTS: Compared with the control group (CG), the utilization of starch and production of ethanol in the inoculated group (IG) increased by 3.55% and 12.59%, respectively. The use of bio-augmented Daqu changed the bacterial communities. For example, Kroppenstedsia was the dominant bacterial genus (the relative abundance was about 22%) in the CG while Lactobacillus was the main dominant genus (the relative abundance was more than 30%) in the IG on days 20-30. Lactobacillus showed a significant positive correlation with the aroma compounds. The use of bio-augmented Daqu increased the aroma compound content - such as the ethyl heptanoate and ethyl hexanoate content. CONCLUSION: The addition of bio-augmented Daqu with A. niger and S. cerevisiae could change microbial communities, resulting in an increase in the yield of ethanol and the aroma compound content of fermented grains, thus improving the quality of baijiu. © 2022 Society of Chemical Industry.
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Microbiota , Odorantes , Odorantes/análise , Fermentação , Bebidas Alcoólicas/análise , Saccharomyces cerevisiae , Bactérias , Lactobacillus , Etanol , ChinaRESUMO
Metformin has potential anti-inflammatory properties and accelerates wound healing by enhancing vascular development. In this study, we aimed to investigate the effects of metformin on pulmonary vascular development and the underlying mechanism. Newborn mice were subcutaneously injected with metformin from day 2 after exposure to hyperoxia. Pulmonary vascular development, inflammation, and Shh signaling pathway-related protein expression were evaluated by western blotting and immunofluorescence staining. M2 macrophage polarization was measured by flow cytometry. The effect of metformin on macrophage polarization was determined using RAW264.7 macrophages exposed to 90% oxygen in vitro. The role of metformin and purmorphamine on M1 and M2 polarization was observed by flow cytometry. M2 polarization of pulmonary macrophages was inhibited after hyperoxic exposure, and metformin increased the number of M2 macrophages in the lung on postnatal day 14. Metformin upregulated CD31 expression and suppressed inflammation in the lung of mice exposed to hyperoxia on postnatal days 7 and 14. Metformin downregulated the Gli1 expression in macrophages in the lung after exposure to hyperoxia on postnatal day 14. In vitro studies showed that metformin inhibited the Gli1 expression in RAW264.7 macrophages exposed to 90% oxygen, which was reversed after purmorphamine pretreatment. Exposure to 90% oxygen inhibited the polarization of M2 macrophages, whereas metformin increased the number of M2 macrophages. Purmorphamine reversed the effects of metformin on M2 polarization and vascular endothelial growth factor (VEGF) upregulation in RAW264.7 macrophages exposed to hyperoxia. In conclusion, metformin regulates macrophage polarization via the Shh signaling pathway to improve pulmonary vascular development in bronchopulmonary dysplasia.
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Displasia Broncopulmonar , Proteínas Hedgehog , Hiperóxia , Macrófagos , Metformina , Animais , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/genética , Polaridade Celular , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Hiperóxia/metabolismo , Inflamação/metabolismo , Pulmão/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metformina/farmacologia , Camundongos , Oxigênio/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismoRESUMO
In this Letter, a new class of an accelerating self-imaging surface plasmonic wave, the Airy-Talbot plasmon, is introduced for the first time, to the best of our knowledge. Our research shows that such a surface wave propagates at the interface between metal (silver) and a dielectric material (air) and causes a strong interference along curved trajectories, which generates the Talbot effect in the surface. The propagation properties have potential value in nanoscale plasmonic devices. A scheme for generating this novel plasmon theoretically is proposed, and we prove it by finite difference time-domain numerical simulations.
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Saccharomyces cerevisiae plays a decisive role in the brewing of alcohol products, and the ideal growth and fermentation characteristics can give the pure flavor of alcohol products. However, S. cerevisiae can be affected profoundly by environmental factors during the brewing process, which have negative effects on the growth and fermentation characteristics of S. cerevisiae, and seriously hindered the development of brewing industry. Therefore, we summarized the environmental stress factors (ethanol, organic acids, temperature and osmotic pressure) that affect S. cerevisiae during the brewing process. Their impact mechanisms and the metabolic adaption of S. cerevisiae in response to these stress factors. Of note, S. cerevisiae can increase the ability to resist stress factors by changing the cell membrane components, expressing transcriptional regulatory factors, activating the anti-stress metabolic pathway and enhancing ROS scavenging ability. Meantime, the strategies and methods to improve the stress- tolerant ability of S. cerevisiae during the brewing process were also introduced. Compared with the addition of exogenous anti-stress substances, mutation breeding and protoplast fusion, it appears that adaptive evolution and genetic engineering are able to generate ideal environmental stress tolerance strains of S. cerevisiae and are more in line with the needs of the current brewing industry.
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OBJECTIVE: To investigate the effects of electrical dry needling (DN) plus corticosteroid injection (CSI) on pain, physical function, and global change in patients with osteoarthritis of the knee (KOA). DESIGN: A prospective, single-blinded, randomized controlled trial. SETTING: Pain treatment clinic. PARTICIPANTS: Sixty patients with KOA were randomly assigned to the electrical dry needling plus corticosteroid injection (electrical-DN+CSI) group or CSI group. INTERVENTIONS: The CSI group received glucocorticoid injection only once during the trial, and the electrical-DN+CSI group received glucocorticoid injection combined with 4 sessions of electrical-DN. MAIN OUTCOMES MEASURES: The primary outcome was the numerical rating scale at 3 months. The secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index, the time to complete the Timed Up and Go test, and the score of the global rating of change scale at 3 months. A generalized linear mixed-effects model was used to analyze the repeated measurement data. RESULTS: Baseline characteristics and measurements were similar in the 2 groups. The group by time interaction effect was significant for all variables (P<.05). The electrical-DN+CSI group obtained a more significant reduction in pain intensity and more significant improvement in dysfunction than the CSI group at 3 months (P<.05). The median global rating of change score for the CSI group was +3 (somewhat better), and that for the electrical-DN+CSI group was +4 (moderately better). CONCLUSION: Electrical-DN therapy at myofascial trigger points combined with CSI is more effective at alleviating pain, improving dysfunction, and creating global change than CSI alone for patients with KOA. Electrical-DN may be an essential part of treatment for KOA rehabilitation.